High levels of blood glucose are thought to be associated with colorectal cancer (CRC) and hyperinsulinemia, an interstage in the development of CRC. The purpose of this study was to examine associations between incident CRC and blood glucose; plasma insulin; and the homeostasis model assessment for insulin resistance (HOMA2-IR), respectively, and to determine whether these associations were dependent on sex and cancer site. The Malmö Diet and Cancer cardiovascular cohort comprises 6103 individuals. During 81,781 person-years of follow-up, 145 cases of CRC were identified. The hazard ratio of measured blood glucose and plasma insulin and calculated HOMA2-IR were estimated with Cox proportional hazard regression. An association was found between high levels of blood glucose and risk of CRC (HR: 1.72 for the highest compared with the lowest quartile; 95% CI: 1.05, 2.84; ptrend = 0.044), and colon cancer (HR: 1.70 for the highest compared with the lowest quartile; 95% CI: 0.87, 3.33; ptrend = 0.032). In men, an association was found between blood glucose and CRC (HR: 2.80 for the highest compared with the lowest quartile; 95% CI: 1.37, 5.70; ptrend = 0.001), and colon cancer (HR: 4.48 for the highest compared with the lowest quartile; 95% CI: 1.27, 15.84; ptrend = 0.007), but this was not found in women. No associations between plasma insulin, or HOMA2-IR, and CRC, were found. High levels of blood glucose in men are associated with risk of colon cancer. The findings contribute to facilitating to identify those most in need of prevention and screening.