Objective: Sleep disturbances are common in major depressive disorder (MDD), although polysomnographic (PSG) abnormalities are more prevalent in adults than in children and adolescents with MDD. Sleep spindle activity (SPA) is associated with neuroplasticity mechanisms during brain maturation and is more abundant in childhood and adolescence than in adulthood, and as such, may be a more sensitive measure of sleep alteration than PSG in early-onset depression. This study investigated SPA changes related to early-onset MDD, comparing individuals already ill with MDD and individuals at high-risk for MDD with healthy nondepressed controls. Method: The study included 63 participants (8 to 15 years of age): 21 currently depressed individuals, 21 individuals at high risk for MDD based on positive family history of MDD, and 21 healthy control individuals with no personal or family history of psychiatric illness. All participants maintained a regular sleep/wake schedule for 5 days, followed by 2 nights in the laboratory. SPA was analyzed in Stage 2 of non-rapid eye movement sleep. Results: SPA differed significantly between groups, particularly in the late part of the night (F[subscript 2,62] = 7.3, p = 0.001). Although the difference was greatest between the MDD and healthy control groups, both the MDD (p = 0.0004) and at high-risk groups (p = 0.02) had significantly lower SPA compared with healthy controls. SPA deficit was more prominent in females than in males (F[subscript 5,62] = 5.19, p = 0.005). Conclusions: Low SPA characterizes youths with MDD and those at high risk for MDD, particularly girls, suggesting that early-onset depression and risk for the MDD are associated with decreased neuroplasticity. (Contains 3 figures and 2 tables.)