In the Season 3 premiere, Jackie's marriage is strained, as is her relationship with O'Hara after the intervention; Akalitus warns the staff that nearby hospitals have closed down, straining the staff and resources; Zoey publicly confesses her affair with Lenny.

Eddie tells Jackie that he now considers Kevin a real friend and can no longer lie to him; Jackie is remorseful when she learns that O'Hara is looking for a new employer; Akalitus announces that All Saints may get a visit from the First Lady.

Kevin's younger sister Tunie visits after a breakup with her boyfriend; Lenny prepares a surprise romantic picnic for Zoey; two street vendors are brought in after a turf war turns violent; Akalitus fights Catholic bureaucrats over the hospital's chapel.

Jackie finds a new hiding place for her pills and buries the hatchet with O'Hara, who becomes ER chief; Zoey works her first double shift; Kevin invites Eddie to a backyard barbecue; Jackie must tell more lies to retrieve her misplaced stash.

Jackie runs out of drugs and Dr. Cooper decides to compete with Dr. O'Hara for the E.R. chief position.

Mrs. Akalitus is in a holy uproar as workers from the archdiocese remove her religious statues. Meanwhile, a new temp nurse makes his presence known in the ER, and some people don't appreciate it; Coop deals with personal, professional and podiatric problems; and Jackie tries to deal with Kevin playing matchmaker between Eddie and his sister.

Kelly wins over the All Saints staff; Kevin finds pills in a dental floss dispenser; a patient soothes Coop's depression; Jackie pockets drugs.

Jackie accuses Kelly of being inappropriate with two flirty high school girls; Coop begins to let go of childish things; Thor counsels Akalitus on her new phone system and some deeper matters; Jackie is unexpectedly delayed getting to Grace'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.

When HR demands urine samples from all the nurses, Jackie tries to avoid it as long as possible as well as her husband, who seems to have found out about her affair with Eddie.