Postoperative bacterial infectious complications are frequent in patients with colorectal cancer (CRC), with subsequent increased recurrence rates and poor prognosis. Deficiency of the mannan‐binding lectin (MBL) complement activation pathway may cause increased risk of infection in certain patient groups. It is hypothesized that a deficient MBL pathway might be more frequent among patients with CRC than in healthy individuals. The MBL pathway was therefore evaluated in serum obtained preoperatively from 193 patients with primary CRC and in serum from 150 healthy volunteers. Serum MBL concentrations and MBL/MASP activity were determined using immunofluorometric assays. The levels are presented as the median, inter‐quartile range and range. Serum MBL levels were significantly (P < 0.0002) increased in patients with colorectal cancer (1384 (400–2188) ng/mL) (median, inter‐quartile range) compared with levels in healthy blood donors (924 (230–1476) ng/mL). Similarly, the MBL/MASP activity was significantly (P < 0.0002) increased in patients (584 (202–914) mU/mL) compared with in blood donors (319 (0–684) mU/mL). This was independent of age, gender, tumour location in the colon or rectum, and disease stages according to Dukes' classification. No statistical difference (P = 0.20) in frequency of MBL deficiency was found between the patients (20%) and the donors (27%). Overall, the MBL complement activation pathway is significantly increased in patients with colorectal cancer compared with healthy persons. However, similar frequencies of MBL pathway deficiency are observed in patients and healthy persons.