Objectives: The purpose of this study was to determine the quality of sleep and its relationship with general health of first-and second-year medical residents of various specialties working in teaching centers affiliated with Iran University of Medical Sciences. Methods: This study was a cross-sectional and descriptive-analytical study. Of 1246 first- and second-year medical residents 330 (56.1% male, 43.9% female with mean age of 31.9) were selected randomly to participate in the study. The data collection instruments included a demographic questionnaire and habits of residents, the Pittsburgh Sleep Quality Index (PSQI), and the General Health Questionnaire-28 (GHQ-28). The data were analyzed using Pearson's correlation coefficient and multi-nominal logistic regression analysis. Results: Mean score of PSQI (±SD) of studied individuals was 6.9±0.5, (median 5). In total 200 persons (60.6%) had scores higher than 5 indicating undesirable sleep quality. Sleep quality scores had relatively strong correlation with subscales’ scores of anxiety and insomnia; and also with GHQ-28 total score (r<0.6; p<0.001). Of all background variables, 8 to 12 shifts per month (adjusted OR=3.360; 95% CI: 1.750 to 6.451) and more than 12 shifts per month (adjusted OR=2.020; 95% CI: 1.007 to 4.053) compared to fewer than 8 shifts per month, and poor general health in GHQ-28 (adjusted OR=9.141; 95% CI: 4.006 to 20.862) compared to adequate general health were related to higher probability of inadequate sleep quality. Conclusion: More than half of the first-and second-year residents were experiencing poor sleep quality and sleep quality had significant and inverse correlation with general health status and number of shifts per month.