Background: This study investigated the prospective association between source-specific workplace social support and high-sensitivity C-reactive protein (hs-CRP) levels in workers in Japan. Methods: We conducted a 1-year prospective cohort study with 1,487 men and 533 women aged 18–65 years. Participants worked at two manufacturing worksites in Japan and were free of major illness. We used multivariable linear regression analyses to evaluate the prospective association between supervisor and coworker support at baseline, and hs-CRP levels at follow-up. We conducted the analyses separately for men and women. Results: For women, high supervisor support at baseline was significantly associated with lower hs-CRP levels at follow-up (β = −0.109, P < 0.01), whereas coworker support at baseline was not significantly associated with hs-CRP levels at follow-up. Associations between supervisor and coworker support and hs-CRP levels were not significant for men. Conclusions: Supervisor support may have beneficial effects on inflammatory markers in working women. Am. J. Ind. Med. 59:676–684, 2016.