Objective Alcohol is a hypnotic that modifies immune function, specifically the cytokines interferon gamma (IFN-γ) and interleukin 2 (IL-2). We evaluated the association between unscheduled napping and acute alcohol-induced augmentation of IFN-γ and IL-2 expression. Methods In this prospective, observational pilot study, volunteers completed questionnaires on sleep quality, alcohol use, and hangover characteristics. Actigraph recordings began three nights before and continued for four nights after study initiation. Napping was recorded by actigraphy and self-reporting. A weight-based dose of 100-proof vodka was consumed, and the blood alcohol content (BAC) and phytohemagglutinin-M stimulated cytokine level were measured before and 20 minutes, 2 hours, and 5 hours after binge consumption. Results Ten healthy volunteers participated (mean age, 34.4 ± 2.3 years; mean body mass index, 23.9 ± 4.6 kg/m2; 60% female). The mean 20-minute BAC was 137.7 ± 40.7 mg/dL. Seven participants took an unscheduled nap. The ex vivo IFN-γ and IL-2 levels significantly increased at all time points after binge consumption in the nappers, but not in the non-nappers. Conclusion Augmented IFN-γ and IL-2 levels are associated with unscheduled napping after binge alcohol consumption. Further studies are needed to clarify the associations among alcohol consumption, sleep disruption, and inflammatory mediators.