Background C‐reactive protein (CRP) is a well‐documented predictor of cardiovascular diseases and mortality. We aimed to better understand the distribution and determinants of CRP in the population. Materials and methods Study participants were men and women aged 40–79 in the UK‐based EPIC‐Norfolk population‐based cohort study. CRP was measured in 18 586 available serum samples (8334 men and 10 252 women) and remeasured in 6087 individuals on average 13 years later using a high‐sensitivity assay. Results In cross‐sectional analyses, the range of serum CRP was 0·1–188·3 mg/L and the median 1·6 mg/L. A third of the population had serum CRP levels above 3 mg/L. Serum CRP levels were comparable in men and women who were not taking postmenopausal hormone replacement therapy (HRT). Women who were taking HRT had double CRP levels compared with HRT nonusers. Smoking was also strongly related to CRP in men and women. Serum CRP was positively and independently associated with age, body mass index and waist circumference and inversely with height. A stronger association with serum CRP measured concurrently than on average 13 years later indicated a short‐term rather than long‐term association with smoking and HRT use. Social class and alcohol intake were not independently related to CRP, but there was a strong inverse association with educational status. Conclusion The distribution of serum CRP in the population is similar in men and women after taking into account smoking and HRT use. Anthropometric factors as well as educational status are strongly related to serum CRP.