Abstract Background: We investigated whether preoperative and postoperative levels of inflammation markers, which have mechanistically been linked to colorectal cancer progression, were associated with recurrence and all-cause mortality in patients with colorectal cancer. Methods: Data of two prospective cohort studies were used. For the current analysis, patients with stage I to III colorectal cancer were considered. Data on inflammation [IL6, IL8, IL10, TNFα, high-sensitivity C-reactive protein (hsCRP), and a combined inflammatory z-score] were available for 747 patients before surgery and for 614 patients after surgery. The associations between inflammation marker levels and colorectal cancer recurrence and all-cause mortality were examined using multivariable Cox proportional hazard regression models, considering patient characteristics and clinical and lifestyle factors. Results: Higher preoperative and postoperative hsCRP levels were associated with a higher risk of recurrence [HRper doubling (95% CI), 1.15 (1.02–1.30) and 1.34 (1.16–1.55)] and all-cause mortality [HRper doubling (95% CI) 1.13 (1.01–1.28) and 1.15 (0.98–1.35)]. A doubling in IL8 levels (preoperative levels HR = 1.23; 95% CI, 1.00–1.53 and postoperative levels HR = 1.61; 95% CI, 1.23–2.12) and a higher combined inflammatory z-score (preoperative HRper doubling = 1.39; 95% CI, 1.03–1.89 and postoperative HRper doubling = 1.56; 95% CI, 1.06–2.28) were associated with a higher risk of all-cause mortality, but not recurrence. No associations between IL6, IL10, and TNFα and recurrence or all-cause mortality were observed. Conclusions: Preoperative and postoperative levels of specific inflammation markers were associated with recurrence and/or all-cause mortality. Impact: The complex role of inflammation in cancer recurrence merits further elucidation by investigating local inflammation at the tumor site.