- Prolonged working hours and sleep deprivation can exert negative effects on professional performance and health. To assess the relationship between sleep deprivation, key metabolic markers, and professional performance in medical residents. We compared 35 residents working the in-house night shift with 35 senior year medical students in a cross-sectional cohort study. The Epworth Sleepiness Scale (ESS) questionnaire was administered and blood tests for complete blood count (CBC), blood chemistry panel, lipid profile and C-reactive protein (CRP) were obtained from all participants. Medical students and medical residents were comparable demographically except for age, weekly working hours, reported weight gain, and physical activity. The ESS questionnaires indicated a significantly higher and abnormal mean score and higher risk of falling asleep during five of eight daily activities among medical residents as compared with medical students. Medical residents had lower high density lipoprotein levels, a trend towards higher triglyceride levels and higher monocyte count than did medical students. CRP levels and other laboratory tests were normal and similar in both groups. Among the residents, 5 (15%) were involved in a car accident during residency, and 63% and 49% reported low professional performance and judgment levels after the night shift, respectively. Medical residency service was associated with increased sleepiness, deleterious lifestyle changes, poorer lipid profile, mild CBC changes, and reduced professional performance and judgment after working the night shift. However, no significant changes were observed in CRP or in blood chemistry panel. Larger prospective cohort studies are warranted to evaluate the dynamics in sleepiness and metabolic factors overtime.