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Nurse Jackie Peyton is a hard working and dedicated ER nurse. She has a bad back, is married with two kids, but fools around and puts altogether too many hours in at work. She also has good judgment and knows more than some of the residents. When she tells Dr. Cooper that she suspects a bicycle messenger brought in following an accident of having a brain bleed, he blows her off. She decides that something good will come out of the situation regardless. Similarly, when she learns that a diplomat who attacked a hooker will not be charged because of his diplomatic immunity, she has a solution for that as well.
Longtime ER nurse Jackie Peyton bends the rules to bring some good from a patient's senseless death, while concealing her addiction to painkillers she gets from her boyfriend, the hospital pharmacist.
Jackie meets a patient who used chicken soup to treat his heart disease. Furthermore, she talks to Dr. O'Hara about her daughter's anxiety and gets to know that a pill-dispensing machine will take Eddie's job.
Jackie and Kevin think about sending their daughter Grace to a private school. Meanwhile, stoic Dr. O'Hara can't escape a boy who wants to thank her for saving his twin brother's life.
A 10-year-old girl needs Jackie's help to care for her mother who suffers from lupus. Furthermore, Mrs. Akalitus manages to taser herself.
When Jackie meets an old friend and fellow nurse who suffers from terminal lung cancer, she is asked to help her commit suicide. A gall bladder attack brings Dr. Cooper's mother to the hospital where she gives away a secret about her son.
After the ex-husband of his date attacked him with a knife, a man is brought to the ER. Meanwhile, Mrs. Akalitus takes care of a foundling who was left at the nurses' station.
When Jackie addresses a temp nurse's drug abuse, he calls her an hypocrite. In the meantime, Mrs. Akalitus is still responsible for the baby left at the station.
Jackie has to deal with the consequences of her drug abuse and Zoey's criticism on Jackie's initial treatment of a patient. Also, Jackie falsifies an organ donor's file.
Jackie has to come up with drastic measures to keep Dr. Cooper from exposing her for falsifying an organ donor's file. Besides, Jackie can't take her wedding ring off when she is about to meet Eddie and seeks Dr. O'Hara's help.
Jackie gets cut off her Percocet supply when Eddie is finally replaced by a pill-dispensing machine. Meanwhile, Zoey makes a mistake and gives a wrong dosis of a painkiller to a film critic who ends up in a coma and Eddie finds out the truth about Jackie's family.
Kevin asks Jackie to meet for a rendezvous at midnight. Eddie threatens to tell the truth about Jackie's family and Dr. O'Hara's mother is brought to the ER.
After breaking up with Eddie, Jackie tries to reconnect with her family. At the hospital, Cooper files a formal complaint against Jackie, the former temp Sam joins the nursing staff and a former employee is brought in with an overdose.
Without Jackie's knowledge, Eddie keeps up his friendship with Jackie's husband Kevin. In the meantime, Jackie has to cover for O'Hara who drank a little too much over her grief.
Grace's friend Kaitlyn walks in on Jackie taking drugs who is forced to come up with a convincing cover story. Meanwhile, Kevin refuses to take O'Hara's financial help and Cooper let's everyone know that he made the list of Manhattan's top 25 doctors.
When a patient is suffering, Jackie supplies the patient with illegal marijuana to ease the pain. Meanwhile, Kevin prefers going out with Eddie rather than spend the night with Jackie and Zoey believes she is pregnant.
Jackie's life gets a little more complicated because of a security guard and O'Hara's longtime affair comes to light.
Unhappy about Eddie and Kevin's friendship, Jackie asks Eddie to stop spending time with Kevin. A pharmaceutical company rep provides Jackie with drugs.
Coop insults the biggest donor of the hospital while Jackie revisits her affair with Eddie.
Coop arranges a date for Georgia and Eddie while Jackie's daughter Grace starts therapy.
Jackie sets up a P.O. box for a secret credit card she uses to pay for prescriptions. When she is deep in debt, she accepts Dr. O'Hara's money for the girls. In the meantime, Mrs. Akalitus is tired of a malfuctioning Pill-O-Matix and offers Eddie his old job back and Grace shows a new sympton of her anxiety disorder.
In order to get a phony prescription, Jackie falsifies an MRI. In the meantime the campaign's end has its effects on Coop and Eddie is back as the hospital's pharmacist.
Before she has to answer some questions to Dr. O'Hara, Jackie and her family leave for a family vacation. Unfortunately, Jackie loses her stash and starts going through withdrawal and Kevin learns that she took O'Hara's money.
With her world crumbling down, Jackie tries for damage control. But after losing Kevin's trust, he starts uncovering her lies.
The intervention Kevin and O'Hara staged has taken its toll on Jackie's relationships with them. Meanwhile, nearby hospitals close down which strains the All Saints Hospital resources and Zoey makes her affair with Lenny public.
Eddie is considering telling Kevin about his affair with Jackie. Meanwhile, Jackie finds out that Dr. O'Hara wants to take a new job.
Kevin's sister stops by to pay Jackie and her family a visit. In the meantime, Lenny makes plans for a romantic picnic for Zoey and Mrs. Akalitus has to deal with Catholic bureaucrats.
Jackie and Dr. O'Hara settle their differences, and Kevin asks Eddie to come to their family barbecue.
Jackie runs out of drugs and Dr. Cooper decides to compete with Dr. O'Hara for the E.R. chief position.
The statues of the saints are finally removed from the chapels. Meanwhile, Jackie clashes with the new nurse named Kelly Slater and Eddie considers going out with Tunie.
The new nurse Kelly charms the hospital's staff except Jackie, meanwhile a patient eases Dr. Cooper's pain who is depressed about the split of his parents. Kevin discovers a secret stash in a dental floss dispenser while Jackie steals drugs from the Oncology.
Jackie criticizes Kelly's interaction with two flirty high school girls while Mrs. Akalitus seeks Thor's help with a new phone system. Jackie can't arrive in time at her daughter's pageant.
Just when Jackie has run out of pills, she runs into a confrontation about the drugs from Oncology that disappeared. Coop tracks down an old girlfriend on Facebook when he decides to start his own family. Heart problems make Zoey revisit her relationship with Lenny.
Following HR's inquiry of the missing drugs, Mrs. Akalitus puts Jackie on probation. Meanwhile, Coop plans his wedding and Jackie's daughter Grace wants to be put on medication for her anxiety disorder.
Jackie tries to stay sober and get through probation until Dr. O'Hara has a tempting offer for her. Meanwhile Eddie believes Kevin found out about the affair and Zoey throws a party for her colleagues.