OBJECTIVE Young adults often encounter sleep deprivation and stressful events. Both have been separately reported to modulate immunity, and occasionally they occur simultaneously. We assessed the combined effects of these conditions on immune competence in healthy students. METHODS Twenty-three participants (mean age 24 years; SD 1.86; 14 females) were exposed to 30 h of sleep deprivation during which they conducted physiological, social and cognitive tasks. The control group consisted of 18 participants (mean age 23.67 years; SD 1.46; 11 females). All participants underwent cognitive and psychological evaluations at 10:00 AM, followed by blood and saliva collection, 3 days before sleep deprivation induction and on the morning following it. Immune/endocrine measures included blood counts of lymphocytes, granulocytes, monocytes and natural killer (NK) cells; levels of several cell surface markers; NK cytotoxicity; plasma levels of interleukin (IL)-6, IL-10, dehydroepiandrosterone and neuropeptide Y, and plasma and salivary cortisol levels. RESULTS Although the experimental protocol significantly elevated state anxiety and psychological dissociation levels, no effects were evident in any of the immunological/endocrine indices. In contrast, expected sex differences in immune measures were found, including significantly higher NK cytotoxicity and monocyte counts in males, validating the integrity of the measurements. CONCLUSIONS The findings suggest resilience of the immune system to a combined sleep deprivation and stressful exposure in young adults, while previous studies reported immune perturbations following either of these conditions separately. These apparent contradictions might reflect differences in the study design or in the methodology used for immunological assessments, including the time of sample collection, the combination of sleep deprivation with stress and our in vivo assessment of cytokine levels.