Abstract This study aimed to analyze the incidence and risk factors of acute anastomotic leak (AL) in patients with colorectal cancer (CRC) during and after the COVID-19 pandemic. Active COVID-19 was evaluated as a risk factor of acute AL. A retrospective multicenter analysis was performed on 390 patients with CRC between April 2020 and October 2024. Patients were divided into acute AL (n = 27) and no acute AL (no AL) (n = 363) groups. In the acute AL group, there were 24 (88.8%) men and three (11.2%) women, with a median age of 63 (65–67) years. Twenty-seven patients in both groups had a previous COVID-19 infection and 15 patients (55.5%) who complained of COVID-19 had AL. The incidence of clinical AL was 6.9% (27/390), of which 11.1% (3/27) and 88.9% (24/27) were grade B and C, respectively. 24/27 (88.9%) had free AL with peritonitis requiring surgical re-intervention. Multivariate analysis showed that active COVID-19 infection (OR = 176, 95% CI 14.27–2172.57, p < 0.001) and serum albumin level < 3 g/dl (OR = 16.249, 95% CI 1.033–255.544, p = 0.04) were associated risk predictors of AL, while the laparoscopic approach (OR = 0.032, 95% CI 0.002–0.434, p = 0.01) and splenic flexure mobilization (OR = 0.022, 95% CI 0.003–4.844, p = 0.02) were protective. The incidence of AL after CRC surgery did not increase during or after the COVID-19 pandemic. Active COVID-19 and serum albumin levels < 3 g/dl were associated risk factors for AL, while the laparoscopic approach and splenic flexure mobilization were protective.