Objectives: The adverse effects of hypoxia and sleep deprivation (SD) have been studied separately but there is little literature on their effects when acting in conjunction. Hence, the effects of SD on hypoxia tolerance and cognitive performance when exposed to altitude were investigated. Material and Methods: In a cross-sectional repetitive measure design, 15 healthy volunteers assessed on cognitive performance were made to perform cognitive tests (Dual Task Test, Stroop Test [ST], and Digit Symbol Substitution Test [DSST] of Psychometric Evaluation Designed for Aviators test battery) on the ground and at a simulated altitude of 17,000 ft in a hypobaric chamber on 4 days. On the 2nd and 3rd day, the tests were done following 2 h of SD the previous night, and on the 4th day, the same was repeated following normal recovery sleep. Heart rate (HR) and respiratory rate (RR) were measured on the ground and 17,000 ft. The Lake Louise Acute Mountain Sickness (LLAMS) scores were used to assess the severity of symptoms of hypoxia and time to arterial oxygen desaturation of 75% was used to measure hypoxia tolerance. Results: Although not statistically significant, the LLAMS scores showed an increasing trend on SD days with an improvement in recovery of sleep. No statistically significant differences in the HR (F = 0.569, P = 0.637) and RR (F = 0.569, P = 0.637) were observed across the days of SD or recovery. The time to oxygen desaturation to 75% also showed no significant effect (F = 0.587, P = 0.625). A statistically significant increase in response times of two cognitive tests (ST and DSST) was observed on exposure to altitude on all 4 days. The three cognitive tests did not show any statistically significant effect following 2 h of SD or recovery. Conclusion: The study could not elicit a statistically significant effect of 2 h of SD across 2 consecutive nights on the cognitive performance measures on exposure to hypoxia.