Objective: To examine the relationship between perceived stress/digital literacy and student satisfaction in health science college students in the distance education process. Method: The cross-sectional study was conducted by collecting data from 842 students. The dependent variable was student satisfaction in distance education. For the analyses, t-test, ANOVA (post hoc: Bonferroni), and linear regression methods were used. Results: Distance education student satisfaction was 178.21 ± 48.64. Student satisfaction was low among those who think that distance education is not more effective than face-to-face education, live in villages/towns, and have high perceived stress. Student satisfaction was high among those who do not have limited internet access, can access the internet via computer, follow the lessons regularly every week, think distance education is applicable in the health domain, can acquire instant feedback from the instructor, and have increased digital literacy. Conclusion: Distance education student satisfaction was found to be moderate. Student satisfaction in distance education increases as perceived stress levels decrease and digital literacy levels increase.