Little is known about the contribution of occupational skin exposure as a risk factor for physician-certified long-term sick leave in the general working population of Norway. This study drew a cohort (n = 12,255; response at baseline 69.9%) randomly from the general population of Norway. Occupational skin exposure (in 2009) was measured based on 5 items. The outcome of interest was physician-certified long-term sick leave ≥ 16 days during 2010. Statistical adjustment for psychosocial and mechanical occupational exposures was performed. Long-term sick leave was predicted by occupational skin exposure to cleaning products (odds ratio (OR) 1.7; 95% confidence interval (95% CI) 1.1–2.5) and waste (OR 2.1; 95% CI 1.1–3.7) among men, and occupational skin exposure to water (OR 1.3; 95% CI 1.0–1.6) among women. The estimated population attributable risk for occupational skin exposure was 14.5%, which emphasizes its contribution as an important risk factor for long-term sick leave.