Objectives: The objectives were to assess the prospective associations between work-related factors, including psychosocial and physical work factors and working time/hours factors, and sickness presenteeism alone or combined with sickness absence. Methods: The study relied on prospective data of a national representative sample of 16 129 employees followed up from 2013 to 2016 in France. Work-related factors were assessed in 2013 and included 20 psychosocial work factors, 4 working time/hours factors and 4 physical work factors. Sickness presenteeism was studied using two items in 2016: the presence and duration of sickness presenteeism within the last 12 months. Weighted Hurdle and multinomial logistic regression models were performed to study the prospective associations between work-related factors at baseline and sickness presenteeism (both presence and duration) and sickness absence at follow-up. Models were adjusted for covariates. Results: Almost all psychosocial and physical work factors were predictive of sickness presenteeism (ORs ranging from 1.30 to 2.07 for men, and from 1.16 to 2.30 for women) but only some of them predicted its duration. Dose-response associations were observed between multiple exposures to these factors and sickness presenteeism. These factors predicted more sickness presenteeism alone or combined with sickness absence than sickness absence alone. Gender differences were observed in these associations, as some associations were found to be stronger among women than among men. Conclusions: There is a need to study sickness presenteeism and sickness absence combined. Prevention oriented towards the psychosocial and physical work environment may contribute to reduce sickness presenteeism and sickness absence.