This study examined the prevalence of common infections among employees in different work schedules. Self-administered questionnaire data from the Maastricht Cohort Study on "Fatigue at Work" (n = 12,140) were used. Job title was used as a matching variable between day and shift workers to control for their different work environment. We used a multilevel analysis of a two-level structure, in which the individual employees (level 1) were nested within job titles (level 2), adjusted for demographics, longstanding disease, health behavior, work-related factors, fatigue and sleep quality. Results from the multilevel analyses showed that, compared to day work, shift work was associated with a higher risk for common infections, with the highest risk in three-shift workers. Compared to day work, shift work was further associated with differences in health, health behavior, sleep, fatigue and perceived job characteristics, factors that may influence the occurrence of infections and should be taken into account in future studies as well.