The impact of working time arrangements (WTA) on health has been studied extensively. Still, little is known about the interrelation between work schedules, working hours, and depressed mood. For work schedules, the underlying assumptions regarding depressed mood refer to a disturbance of social and biological rhythms, whereas for working hours, the assumptions relate to workload and work capacity. Conversely, depressed mood may urge an employee to adjust his/her work schedule and/or number of working hours/week (h/wk). The aim of this study was to assess the association between work schedule and working hours with depressed mood. Using baseline data from the Maastricht Cohort Study, depressed mood in day work was compared with depressed mood in different shiftwork schedules (n = 8843). Within day work, several categories of working h/wk were studied in association with depressed mood (n = 7217). The association between depressed mood and several aspects of overtime was assessed separately. Depressed mood was measured with a dichotomous item: "Did you feel down every day over the last two weeks?" Separate logistic regression analyses were conducted for men and women, with adjustments for potential confounders. The odds ratio (OR) for depressed mood was greater for men involved in shiftwork than for men only involved in day work (three-shift OR = 2.05 [95% confidence interval, CI 1.52-2.77]; five-shift OR = 1.34 [95% CI 1.00-1.80]; irregular-shift OR = 1.79 [95% CI 1.27-2.53]). In female employees, five-shift work was associated with a higher prevalence of depressed mood (OR = 5.96 [95% CI 2.83-12.56]). Regarding the number of working h/wk, men working <26 h/wk had a higher prevalence of depressed mood than men working 36-40 h/wk (OR = 2.73 [95% CI 1.35-5.52]). After conducting trend analyses, a significant decreasing trend was found in men, whereas an increasing trend was found in women working a high number of hours. Furthermore, a dose-response relationship was present in men regarding the number of overtime h/wk. This study showed that different work schedules and working hours are associated with depressed mood. Shiftwork was related to a higher prevalence of depressed mood than day work. The association was more pronounced for male employees. Regarding the number of working h/wk, male and female employees showed an opposite trend in depressed mood. Because of the possibility of a healthy worker effect and the possibility of a reciprocal relationship between WTA and depressed mood, the reported relation might be underestimated. This study has illustrated that occupational physicians, who deal with depressed mood among workers, should carefully consider the impact of WTA.