This study was to investigate whether the time to the lowest postoperative CEA can predict cancer survival. We enrolled 155 rectal cancer patients in this retrospective and longitudinal cohort study. Deepness of response (DpR) of CEA refers to the relative change of the lowest postoperative CEA level from baseline, and time to DpR (TTDpR) refers to the time from surgery to the lowest postoperative CEA level. The median of TTDpR and DpR was 4.5 (range, 3.0-18.0) weeks and -67% (range, -99% to 114%) respectively. Patients with TTDpR </ = 4.5 weeks had better 3-year DFS (81.4% vs. 76.2%; P = 0.059) and OS (95.8% vs. 87.9%; P = 0.047) rate than patients with TTDpR >4.5 weeks. Using TTDpR as a continuous variable, the HR of DFS and OS was 1.13 (95% CI 1.06-1.22, P = 0.001) and 1.17 (95% CI 1.07-1.29, P = 0.001) respectively. On multivariate analysis, the predictive value of prolonged TTDpR remained [adjusted HRs: 1.12 (95% CI 1.03-1.21, P = 0.006) and 1.17 (95% CI 1.06-1.28, P = 0.001)]. These findings remained significant in patients with normal preoperative CEA. Our results showed prolonged TTDpR of CEA independently predicted unfavorable survival outcomes, regardless of whether preoperative CEA was elevated or not.