As Christmas 1938 approaches, the staff at the Nightingale Hospital have their own wishes for the festive season. Ward sister Frannie Wallace is hoping she won't have to live through another war like the one that claimed her fiance. Staff Nurse Helen Dawson wants to find happiness again after the death of her husband Charlie. But is she looking for love in the wrong place? Matron Kathleen Fox struggles to keep up morale.

It's Christmas 1941, and the nurses at the Nightingale are facing their toughest winter yet. With shortages everywhere and every news bulletin announcing more losses, the British people are weary and demoralised, and The Nightingale Hospital is suffering too. Millie is recently widowed and dealing with the demands of her family's estate. It's not long before her old world of the Nightingale begins to beckon, along with a long-lost love.... Jess is struggling with her move from East London to the countryside.

Dora and her old enemy Lucy are paired up on the children's ward for the final three months of their training. The two nurses couldn't seem more different, but they may have more in common than they think, as each hides a secret heartache. And there are new faces. Jess is the feisty eldest daughter of a notorious East End family and determined to prove herself as a ward maid. New trainee nurse Effie can't wait to escape her small Irish village, and make her way as a nurse in London.

With her husband, Nick, away fighting, Dora struggles to keep the home fires burning but finds herself in a difficult position when she is put in charge of a ward of injured German POWs. Can she find it in her heart to care for her enemies? Fellow nurse Kitty faces a similar struggle looking after the men who killed her beloved brother. But her life becomes even more complicated when she falls for one of the prisoners. And Helen Denton returns from nursing in Europe with a secret. She has her own reasons for hating the Germans.

Matron Kathleen Fox has the job of putting the hospital back together but wonders if she is up to the task. In an attempt to bring some festive cheer, she decides to put on a Christmas show. The idea is greeted with mixed feelings by the nurses, who all have their own problems, and also by the new Assistant Matron and ward sister, who find themselves rivals for the role of organiser. But as rehearsals begin, the performers begin to find the show is not just a tonic for the patients.