Our aim was to assess the internal consistency and structural/construct validity of the Center for Epidemiological Studies Depression Scale among middle-aged employees in Japan. We conducted a cross-sectional study of 7284 workers, aged 49.0 ± 6.3 (mean ± SD) years old. Structural/construct validity was assessed by confirmatory factor analysis. The 4-factor structure reported in the general population was replicated, and a second-order model with an overarching depression factor fitted well. These findings indicate that the Center for Epidemiological Studies Depression Scale is a valid and reliable measure of depressive symptoms for middle-aged workers in Japan.