Objective To study the diagnostic and prognostic value of serum soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) and cyclooxygenase-2 (COX-2) in abdominal infection-caused sepsis. Methods A total of 170 patients with abdominal infection treated in the First Hospital of Qinhuangdao between January 2019 and March 2022 were retrospectively selected and divided into sepsis group (n=76) and non-sepsis group (n=94) according to whether they were combined with abdominal infection-caused sepsis. In addition, 80 healthy people in the same period were selected as the control group. The levels of serum sTREM-1 and COX-2 in the three groups were detected and the differences were compared. The laboratory indexes, including white blood cell count, high-sensitivity C-reactive protein, and procalcitonin of patients with abdominal infection-caused sepsis were detected. The Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation System Ⅱ and prognosis (survival or death) of patients with abdominal infection-caused sepsis were evaluated. The correlations of serum sTREM-1 and COX-2 with the severity of sepsis were analyzed, and the diagnostic and prognostic value of sTREM-1 and COX-2 in abdominal infection-caused sepsis was assessed. Results The levels of serum sTREM-1 and COX-2 in the sepsis group were higher than those in the control group and the non-sepsis group (P<0.05). The levels of serum sTREM-1 and COX-2 in the sepsis group were positively correlated with white blood cell count, high-sensitivity C-reactive protein, procalcitonin, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation System Ⅱ score (P<0.05). The serum levels of sTREM-1 and COX-2 of patients who died during hospitalization in the sepsis group were higher than those of the surviving patients. The areas under the receiver operating characteristic curves of the serum sTREM-1 and COX-2 levels for diagnosing sepsis caused by abdominal infection were 0.814 [95% confidence interval (CI) (0.746, 0.882), P<0.001] and 0.848 [95%CI (0.788, 0.905), P<0.001], respectively, with critical values of 1.879 pg/mL and 18.75 ng/mL, respectively, and those for predicting the prognosis of patients with sepsis caused by abdominal infection were 0.775 [95%CI (0.659, 0.890), P<0.001] and 0.784 [95%CI (0.679, 0.889), P<0.001], respectively, with critical values of 2.283 pg/mL and 23.02 ng/mL, respectively (P<0.05). Conclusion The serum levels of sTREM-1 and COX-2 have certain value in the diagnosis and prognosis prediction of abdominal infection-caused sepsis.