Objective To investigate the role of neutrophil to lymphocyte ratio (NLR) combined with C reactive protein to albumin ratio (CAR) in predicting postoperative anastomotic leakage (AL) in patients with rectal cancer. Methods The clinical data of 187 rectal cancer patients who underwent surgery in Department of General Surgery, the First Medical Center, Chinese PLA General Hospital from Aug. 2016 to Aug. 2020 were retrospectively analyzed. Patients were divided into AL group (27 cases) and non-AL group (160 cases), and NLR and CAR were compared between the 2 groups at different time points. Receiver operating characteristic (ROC) curve was used to evaluate the prediction value of NLR, CAR, and their combination for AL. Multivariate logistic regression analysis was used to explore the independent risk factors of postoperative AL in patients with rectal cancer. Results The NLR of rectal cancer patients in the AL group was significantly higher than that in the non-AL group on the 3^rd day and 5^th day after surgery (P<0.05 and P<0.001), and the CAR was significantly higher than that in the non-AL group on the 5^th day after surgery (P<0.001). ROC curve analysis showed that the area under curve (AUC) value of NLR combined with CAR on the 5^th day after surgery for predicting AL in rectal cancer patients was 0.814, and the AUC values of NLR on the 3^rd day and 5^th day after surgery and CAR on the 5^th day after surgery were 0.652, 0.746 and 0.789, respectively. The AUC value of NLR combined with CAR on the 5^th day after surgery was significantly higher than that of NLR on the 3^rd day after surgery (P=0.03). Multivariate logistic regression analysis showed that drinking history, NLR ≥ 5.610 on the 3^rd day after surgery, NLR ≥ 11.259 on the 5^th day after surgery, and CAR ≥ 2.447 on the 5^th day after surgery were independent risk factors for AL in rectal cancer patients (all P<0.05). Conclusion NLR combined with CAR on the 5^th day after surgery, NLR on the 3^rd day after surgery, NLR on the 5^th day after surgery and CAR on the 5^th day after surgery have predictive value for postoperative AL in rectal cancer patients, and NLR combined with CAR on the 5^th day after surgery has the best predictive effect.