Abstract Background Exposure to shift work has been associated with negative health consequences, although the association between shift work and sickness absence remains unclear. The aim of this study is to investigate associations between cumulative exposure to shift work and sickness absence among ground staff employees of an airline company. Methods This study used data from the MORE (Monitoring Occupational Health Risks in Employees) cohort, which is a 5-year historic cohort. The population of the present study consisted of 7562 ground staff employees. For each employee, work schedules and sickness absence days between 2005 and 2009 were obtained from company records. For the exposure to different shift schedule types and to the cumulative number of night shifts, the association with long-term sickness absence (>7 consecutive sickness absence days) and the number of sickness absence episodes during 2009, was calculated using logistic and Poisson regression analyses. Socio-demographic variables, work-related variables, job classification variables, and previous sickness absence days were regarded as confounders. Results After adjusting for previous sickness absence and job classification variables, only the group of employees that switched into working in a three-shift schedule, showed a significantly increased risk for long-term sickness absence (OR = 1.31, 95%CI 1.02–1.69). Night shift exposure was not significantly associated with long-term sickness absence. Exposure to shift work was negatively associated with more sickness absence episodes. Employees who were exposed to more than 46 night shifts also showed a lower risk for more sickness absence episodes. Subgroup analyses showed that single employees and employees without children had an increased risk for long-term sickness absence when exposed to a three-shift schedule, and when they had changed between shift schedule types. Conclusions Cumulative exposure to shift work proved to be negatively associated with more sickness absence episodes, and was not associated with more long-term sickness absence, although selection bias could not be ruled out. Future research should explore the influence of household composition, and take into account both previous sickness absence and psychosocial and physical work factors to obtain a better estimation of the association between shift work and sickness absence.