Diurnal mood variations are one of the core symptoms in depression, and total sleep deprivation (SD) can induce rapid, short-lasting clinical improvement in depressed patients. Here, we investigated if differential sleep pressure conditions impact on subjective mood levels in young women with major depressive disorder (MDD) without sleep disturbances, and in healthy controls. Eight healthy and eight MDD women underwent 40-h SD (high sleep pressure) and 40-h multiple NAP (low sleep pressure) protocols under constant routine conditions during which subjective mood was assessed every 30-min. MDD women rated overall significantly worse mood than controls, with minimal values for both groups during the biological night (ca. 4 a.m.), under high and low sleep pressure conditions. During SD, nighttime mood ratings in MDD women were lower than in controls and partially recovered during the second day of SD, but never attained control levels. The degree of this diurnal time-course in mood under SD correlated positively with sleep quality in MDD women. Our data indicate that MDD women without sleep disturbances did not exhibit a SD-induced antidepressant response, suggesting that the mood enhancement response to sleep deprivation might be related to the co-existence of sleep disturbances, which is an association that remains to be fully established.