The aim of this study was to examine the relation between sleep difficulty and white blood cell (WBC) count in shift workers. This was a cross-sectional study in male Japanese workers at a synthetic fiber plant. The subjects were 212 male workers who underwent an annual workplace health checkup in April 2007. For the WBC count the blood test value from the health checkup was used. With regard to insomnia, subjects were asked the first 5 of the 8 questions on the Athens Insomnia Scale (AIS). An increased WBC count was associated with total AIS score (p<0.05) and work pattern (shift work) (p<0.05) in addition to smoking (p<0.001), fasting blood sugar (p<0.01), and BMI (p<0.05). In shift workers, the WBC count was related with total AIS score (p<0.05) and those with higher total AIS score tended to have an increased WBC count (p<0.01). In daytime workers, the count was not associated with AIS score. The present results have shown that shift workers with sleeping problems are more likely to have higher WBC counts, which might suggest low-grade inflammatory changes in those workers. Quality sleep may be necessary for shift workers in particular.