Objective The objective of this study was to examine the impact of acute total sleep deprivation (24 hours) and subsequent recovery interventions (caffeine intake or a short nap) on subjective sleepiness, perceived cognitive difficulty, cardiovascular responses, and heart rate variability (HRV) parameters. Additionally, the moderating role of sex in these physiological and perceptual responses was evaluated. Methods A randomized controlled design was employed involving thirty healthy young adults (15 females, 15 males; mean age = 19.9 ± 1.5 years), who were allocated to one of three groups: caffeine, nap, or control. Each participant underwent three repeated assessments—baseline, post-sleep deprivation, and post-intervention. Measurements included the modified Karolinska Sleepiness Scale (mKSS), visual analog scales for task difficulty, systolic and diastolic blood pressure (SBP/DBP), and a range of HRV indices. Data were analyzed using linear mixed-effects models to account for repeated measures and individual variability. Results Sleep deprivation significantly increased subjective sleepiness and cognitive task difficulty, with more pronounced effects in females. Caffeine was more effective than napping or no intervention in reducing sleepiness. Across all sessions, females consistently reported higher task difficulty. Males showed elevated blood pressure under both rest and stress conditions. Caffeine attenuated stress-induced systolic blood pressure increases, especially among males. HRV analysis revealed increased sympathetic activity (LF) and decreased parasympathetic modulation (HF) after sleep deprivation. Group × sex and time × sex interactions for HRV indicated sex-specific recovery patterns. Parasympathetic activity recovered more in males who consumed caffeine, while napping reduced sympathovagal imbalance in both sexes. Conclusion The findings indicate that acute sleep deprivation adversely affects both cognitive and autonomic functioning, with sex-specific differences modulating the magnitude of these effects and the efficacy of subsequent interventions. While caffeine and short naps were each found to offer partial recovery benefits, their mechanisms and effectiveness appeared to vary by sex. These results underscore the importance of personalized fatigue countermeasures in high-demand or safety-critical settings.