BACKGROUND Studies on the epidemiology of sepsis in intensive care units (ICUs) of prefecture-level hospitals in China are rare. This study aimed to investigate the epidemiological characteristics and mortality risk factors of sepsis in ICUs of tertiary hospitals in Sichuan, China. MATERIAL AND METHODS In this prospective, multicenter, observational study, patients admitted to the ICU of 7 tertiary hospitals in Sichuan (China) between October 10, 2017 and January 9, 2018 were screened for sepsis using the Sepsis-3 criteria. Patients with sepsis were included. RESULTS Of the 1604 patients screened for sepsis, 294 (18.3%) had sepsis, and 140 (47.6%) had septic shock. Of these, 169 (57.5%) died. Multivariable analysis showed that central nervous system dysfunction (odds ratio [OR]=2.59, 95% confidence interval [CI]: 1.15-5.84, P=0.022), lowest blood phosphorus level (OR=2.56, 95% CI: 1.21-5.44, P=0.014), highest lactate level (OR=1.20, 95% CI: 1.10-1.32, P<0.001), 24-h Acute Physiologic Assessment and Chronic Health Evaluation-II (APACHE-II) score (OR=1.08, 95% CI: 1.03-1.13, P=0.002), and lung infection (OR=2.57, 95% CI: 1.30-5.09, P=0.007) were independently associated with mortality in patients with sepsis. CONCLUSIONS The prevalence and mortality rates of sepsis are high in tertiary hospital ICUs in Sichuan, China. The APACHE-II score on day 1 after diagnosis, acute central nervous system dysfunction, lowest blood phosphorus, high serum lactate, and lung infection were independent risk factors of mortality in patients with sepsis.