Introduction Given the high incidence of carpal tunnel syndrome in the working population and the co-exposure of workers, it is necessary to improve knowledge of the joint effects of physical and chemical exposures in order to improve prevention strategies. The aim of this study was to assess the prevalence of occupational exposure and co-exposure to physical constraints and neurotoxic chemicals. Methods The study sample was composed of 26,444 workers included in the French cross-sectional survey SUMER 2017s. Occupational exposure within the previous week of work were assessed using a questionnaire during face-to-face interviews with occupational physicians. Four physical constraints were studied: manual handling of loads, forceful joints exertion, repetitive movement and hand-arm transmitted vibrations. Nineteen neurotoxic chemicals were studied: perchloroethylene, trichloroethylene, white-spirit, formaldehyde, etc. Analyses were conducted using weighted data. Results Approximately 24% of men and 11% of women were exposed to at least one physical constraint, and 14% of men and 12% of women were exposed to at least one neurotoxic chemical. About 6% of men and 3% of women were co-exposed to physical constraints and neurotoxic chemicals. Male and female workers under 30 years old and blue-collar workers were more co-exposed than other workers. Male workers in the construction were more co-exposed than other male workers. Discussion Despite the frequency of co-exposures, very few data are available in the literature on the combined effects of physical and neurotoxic chemical exposures on the risk of CTS. Conclusion Occupational co-exposure to physical constraints and neurotoxic chemicals was observed in a significant proportion of French workers.