BACKGROUND: The evidence of sex disparity in acute respiratory distress syndrome (ARDS) is scarce and varies widely. OBJECTIVE: This observational, retrospective study aimed to determine the effect of sex on the sepsis-related ARDS and other short outcomes in critically ill patients with sepsis. METHODS: A total of 2111 adult patients with sepsis who were admitted to three central intensive care units (ICUs) of Wuhan Tongji Hospital between 2012 and 2022 were included in our analysis. Sex was considered as an exposure factor, with sepsis-related ARDS as the primary outcome, and in-hospital mortality, invasive mechanical ventilation(iMV) support, septic shock, and other complications as secondary outcomes. RESULTS: Among the 2111 enrolled patients, 1287 were males (61%) and 824 were females (39%). The incidence of sepsis-related ARDS was higher in males compared to females (P = 0.001), as well as in-hospital mortality (P = 0.009). Multivariate logistic analysis demonstrated that male sex remained independently associated with an increased risk of sepsis-related ARDS (adjusted odds ratio(aOR) = 1. 493[1.034-2.156], P = 0.032). Propensity score matching analysis also indicated that males had 58% higher odds of developing sepsis-related ARDS (aOR = 1.584 [1.022-2.456], P = 0.040). Regarding secondary outcomes, male sex was identified as a risk factor for in-hospital mortality (aOR = 1.536 [1.087-2.169], P = 0.015) and iMV support (aOR = 1.313 [1.029-1.674], P = 0.028) in the fully adjusted model. Sensitivity analysis that included postmenopausal females and age-matched male counterparts showed that male sex still remained to be a risk factor of developing sepsis-related ARDS (aOR = 1.968 [1.241-3.120], P = 0.004). CONCLUSION: Male sex was identified as an independent risk factor for sepsis-related ARDS and in-hospital mortality among critically ill patients with sepsis. Given the retrospective design of this study, the relationship between sex and sepsis-related ARDS requires further validation through large-scale randomized controlled trials in the future.