- Abstract Sleep deprivation (SD) in the early aftermath of stress exposure at the onset of the inactive (resting)-phase, has been shown to ameliorate stress-related sequelae. We examined whether this effect is affected by the temporal proximity between SD and the stressful event or whether it was related to the prevention of sleep in the first resting phase following the exposure. Rats were exposed to stress at the onset of their active phase. Then, they were prevented from sleeping immediately thereafter [forced wakefulness (FW)], or during the first resting phase (SD). The behavior in the elevated plus-maze and acoustic startle response paradigms were assessed seven days post-exposure for retrospective classification into behavioral response groups. We found that resting phase SD (with or without FW) decreased PTSD-like phenotype, whereas immediate FW had no significant effect. The long-term anxiolytic effects of SD appear to stem from a diurnal cycle-dependent mechanism, such that preventing sleep during the first natural resting phase following the traumatic exposure is beneficial in preventing the traumatic sequelae.