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Sepsis, acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS) are severe conditions commonly seen in the intensive care unit (ICU). The study was designed to evaluate the influence of single-organ dysfunction (AKI or ARDS) and 2-organ dysfunction (AKI combined with ARDS) on the 30-day mortality risk in patients with sepsis. Data originated from a prospective multicenter cohort involving 18 Chinese ICUs, which enrolled patients with sepsis following ICU admission. Patients were stratified into 4 groups according to their organ status within 7 days of sepsis onset: those who did not develop AKI or ARDS (non-AKI and non-ARDS group), those who developed AKI but not ARDS (AKI and non-ARDS group), those who developed ARDS but not AKI (ARDS and non-AKI group), and those who developed both AKI and ARDS (AKI and ARDS group). The primary endpoint was defined as mortality within 30 days of sepsis diagnosis. Furthermore, a survival analysis was conducted among the 4 groups. A total of 2175 septic patients were eligible, including 273 cases (12.6%) in the non-AKI and non-ARDS group, 435 cases (20.0%) in the AKI and non-ARDS group, 560 cases (25.7%) in the ARDS and non-AKI group, and 907 cases (41.7%) in the AKI and ARDS group. Kaplan-Meier analysis revealed that the survival probabilities of the 4 groups at 30 days after sepsis diagnosis were 85.6%, 70.6%, 58.9%, and 50.8%, respectively (P < .001). Compared with the patients in the non-AKI and non-ARDS group, a landmark analysis showed that the average adjusted hazard ratios for the 30-day mortality risk for the AKI and non-ARDS, ARDS and non-AKI, and AKI and ARDS groups were 2.19 (95% confidence interval [CI]: 1.26-3.82, P = .006), 2.92 (95% CI: 1.73-4.93, P < .001), and 3.09 (95% CI: 1.85-5.15, P < .001), respectively. Septic patients complicated with AKI and ARDS had a poor prognosis, with a 30-day survival rate of only 50.8% after the diagnosis of sepsis.