Introduction: Khat (Catha edulis) is widely used in East Africa and the Middle East, often in combination with tobacco smoking. Sleep disturbance has been linked with habitual khat use; however, no systematic attempt has been made to test the hypothesis that use of khat and khat and tobacco in combination are related to sleep disturbance. Sleep disturbances are associated with dysregulations in emotional and physiological functions and can increase health risks. Methods: We developed and used the Arabic version of the Pittsburgh Sleep Quality Index (PSQI) to conduct a cross-sectional study in Yemen examining subjective sleep quality in 151 concurrent users of khat and tobacco, 141 khat-only users, and 92 nonusers. Measures on subjective mood were also collected. A series of analyses of variance and χ tests were conducted to test whether khat and tobacco use was linked with sleep disturbances. Results: Concurrent users of tobacco and khat and khat-only users showed greater sleep disturbances than nonusers as assessed by the PSQI global scores (all P values < .001) and component scores. PSQI scores were correlated with negative and positive mood (all P values < .004). Conclusion: Sleep disturbances may be 1 mechanism of the link between khat, tobacco, and negative health outcomes. Our findings may be useful in developing targeted prevention and harm-reduction strategies to minimize health care burdens associated with these substances. Our study also provides initial support for the Arabic version of PSQI.