In Locked In, San Francisco private eye Sharon McCone was shot in the head and suffered from locked-in syndrome: almost total paralysis but with an alert, conscious mind. Now, as Sharon struggles to regain control over her body, she wants everything to go back to normal, but realizes that it may not be possible to return to her old life. Meanwhile, Sharon's relationships are suffering. Her husband is impatient with her refusal to accept help and some of her colleagues doubt her abilities after the accident.

But when Sharon's friend from physical therapy goes missing, she must call upon those closest to her to find out the truth behind the disappearance. The investigation soon points to issues of national security and proves to be the most dangerous and critical case yet for Sharon and her colleagues.