Whether chronic inflammation mirrored by high levels of systemic inflammatory markers such as high sensitive-CRP (hs-CRP) and white blood cell count (WBC) are associated with prostate cancer development remains unclear. In the Prostate Cancer Study throughout Life (PROCA-life), a prospective population-based cohort study, 7,356 men were included. Prediagnostic WBC and hs-CRP were assessed from blood collected at study entry; 2,210 participants also had a second CRP measure during follow-up. During a mean 11.8?years follow-up, 509 men developed prostate cancer (mean age at diagnosis 71.7?years). Multivariable Cox proportional hazard regression models were used to study whether individual biomarkers (WBC, hs-CRP), a combined score based on analyte tertiles (score range 2-6), or change in CRP were associated with risk and severity of prostate cancer. We observed a positive dose-response relationship between hs-CRP and prostate cancer risk with a Hazard Ratio (HR) per mg/l of 1.3, 95% CI 1.00-1.07. Men with an increase in hs-CRP between two measurements (?hs-CRP) of =1.00?mg/l had a 36% increased risk of prostate cancer (HR 1.36, 95% CI 1.02-1.82), compared to men with no change or decrease in hs-CRP. Men with a systemic inflammatory score of 5 or 6 had a 68% higher risk of being diagnosed with metastatic disease (HR 1.68, 95% CI, 1.04-2.73) compared to men with lower scores. Our study supports that hs-CRP including repeated measurements alone or in combination with WBC may be a useful inflammation-related biomarker for prostate cancer risk and prognosis.