Purpose: There is uncertainty over the effect of systemic inflammatory response on oncologic outcomes in patients who underwent neoadjuvant chemoradiotherapy and surgery for rectal cancer. We investigated the association between neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) as markers of systemic inflammation and tumor response and prognosis after treatment. Methods: A total of 176 patients who underwent neoadjuvant chemoradiotherapy and curative surgery for rectal cancer were analyzed retrospectively. Pretreatment hematologic parameters and the main clinical factors for patients and tumors were investigated with respect to their relationship with tumor regression and survival. Results: In the receiver operating characteristic analysis, NLR 2.0 and PLR 133.4 had the highest sensitivity and specificity in predicting tumor response. NLR <2.0 and PLR <133.4 were significantly correlated with good tumor response (odds ratio [OR] 2.490, 95% confidence interval [CI] 1.264–4.904, p = .008; OR 3.009, 95% CI 1.477–6.127, p < .001). Patients with NLR <2.0 had significantly better 5-year disease-free survival rate and overall survival rate compared to patients with NLR ⩾2.0 in multivariate analysis (86.8% vs 70.7%, p = .014; 92.4% vs 71.9%, p = .027). Conclusions: Elevated NLR and PLR levels can be considered as predictors of poor pathologic response, and NLR can be considered a prognosticator in patients who underwent neoadjuvant chemoradiotherapy for locally advanced rectal cancer.