BackgroundDepression, anxiety, and stress levels are considered important indicators for mental health. Khat chewing habit is prevalent among all segments of Jazan population in Saudi Arabia. Few studies have been conducted to evaluate depression, anxiety, and stress among Jazan University students, and information about the correlation between khat use and these disorders is scarce. Thus, this study aims to evaluate the prevalence of depression, anxiety, and stress and their correlation with khat chewing and other risk factors among Jazan University students.MethodsA cross-sectional study was conducted on 642 students from Jazan University. Multistage sampling was used, with probability proportional to size-sampling technique. The Depression, Anxiety, and Stress Scale 21 questionnaire was used to collect the data, which were analyzed using SPSS Version 20.0 software.ResultsModerate depression was prevalent among 53.6% of the sample, anxiety was found among 65.7%, while 34.3% of the students suffered from stress. Female gender was strongly associated with higher mean scores for symptoms of depression, anxiety, and stress, with P-values <0.05 for all. Moreover, anxiety symptoms scores were statistically associated with grade point average and caffeine consumption. Khat use was statistically associated with higher mean scores of anxiety among males and a higher mean score of depression and anxiety among females.ConclusionThe results indicate a high rate of symptoms of depression, anxiety, and stress among Jazan University students. Khat use was associated with anxiety, and a higher rate of symptoms of depression, anxiety, and stress was indicated among female students. Therefore, strategy for the prevention and management of depression, anxiety, and stress is highly recommended to minimize the impact of these serious disorders.