We investigated the possible effect of the 3111T/C CLOCK gene polymorphism on sleep disorders in a sample of 620 patients affected by major depressive disorder (MDD) and bipolar disorder (BP). We detected a significantly higher recurrence of initial (P = 0.0001), middle (P = 0.0009), and early (P = 0.0008) insomnia in homozygotes for the C variant and a similar trend concerning decreased need of sleep in BP (P = 0.0074). Other demographic and clinical features were found not related with CLOCK polymorphisms. This preliminary observation leads to hypothesize a possible involvement of the CLOCK gene polymorphism in the sleep disregulations in MDD and BP.