The aim of this study was to investigate the cross-sectional and longitudinal effect of job insecurity on common infections and health complaints. Self-administered questionnaire data from the Maastricht Cohort Study (n = 12, 140) were used. We used Generalized Estimating Equations analyses to calculate pooled odds ratios (ORs) and 95% confidence intervals. A cross-sectional relationship between job insecurity and common infections or health complaints was found. For the longitudinal relationship, the largest effect was found for flu-like illness (OR 1.39; CI = 1.22-1.57) and health complaints (OR 1.51; CI = 1.39-1.64). We additionally corrected for health behavior, the presence of a long-standing illness, and work-related demands, resulting in lower ORs. An increase in common infections or health complaints has a substantial impact on employee well-being and may result in economic consequences for the company.