OBJECTIVE: To explore the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) combined with a PD-1 antibody in improving complete clinical response (cCR) and organ preservation in patients with ultra-low rectal cancer. METHODS: This was a prospective phase II, single-arm, open-label trial. Patients with confirmed pMMR status T 1-3a N 0-1 M 0 retcal adenocarcinoma were included. Long-course chemoradiotherapy was delivered to a dose of 50 Gy. A PD-1 antibody was added 2 weeks after the first radiotherapy session, and two courses were administered. After chemoradiotherapy, CapeOX plus PD-1 antibody was administered to patients for two cycles. After evaluation, patients with cCR were managed with a watch-and-wait (W&W) approach. Local excision or a W&W approach was performed for patients with near complete clinical response (ncCR) as per multidisciplinary team decision. Radical surgery was recommended for poorly regressed or progressed tumors. RESULTS: Twenty-five patients were enrolled, but two patients withdrew from the study. A total of 23 patients completed the entire neoadjuvant therapy. Ten and five patients achieved cCR and ncCR, respectively, and the rest had a partial clinical response. Patients with cCR were managed with W&W. Four patients with ncCR underwent local excision and were managed using W&W. Eight patients with partial clinical response underwent anus-preserving surgery. At the last follow-up, the rectum and anus preservation rates were 63.4% (14/22) and 95.5% (21/22), respectively. CONCLUSION: nCRT combined with immunotherapy tended to achieve better cCR and rectum preservation rates with good tolerance in patients.