Objectives The extent to which work hours and sleep are associated with self-rated health (SRH) was investigated in full-time employees of small- and medium-scale businesses (SMBs) in a suburb of Tokyo. Methods A total of 2,579 employees (1,887 men and 692 women), aged 18–79 (mean 45) years, in 296 SMBs were surveyed using a self-administered questionnaire from August to December 2002. Work hours, sleep, and SRH were evaluated. Results Compared with those working 6–8 h/day, participants working >8 to 10 h/day and >10 h/day had significantly higher odds of suboptimal SRH adjusted odds ratio (aOR) 1.36 and 1.87, respectively. Similarly, compared with those sleeping 6+ h/day and sufficient sleep, participants with short sleep (<6 h/day) and insufficient sleep had increased odds of suboptimal SRH (aOR 1.65 and aOR 2.03, respectively). Combinations of the longest work hours with short sleep (aOR 3.30) or insufficient sleep (aOR 3.40) exerted synergistic negative associations on SRH. Conclusions This study suggests that long work hours and poor sleep and its combination are associated with suboptimal SRH.