Sex hormones have diverse immunomodulatory effects that may be involved in the pathogenesis of sepsis. However, the roles of serum sex hormones in predicting outcomes and the severity of organ dysfunction, especially acute kidney injury (AKI), in septic shock patients remains controversial. We prospectively enrolled 107 clinically diagnosed pneumonia-related septic shock patients and serum sex hormone levels were measured on the day of shock onset. The aim of the present study was to investigate the predictive values of serum sex hormones levels for 28-day mortality and organs dysfunction, especially AKI. Compared with survivors, serum levels of progesterone (p<0.001) and estradiol (p<0.001) were significantly elevated in non-survivors. In multivariate Cox regression analysis, serum level of estradiol >40 pg/mL (p = 0.047) and APACHE II score ≥25 (p = <0.001) were found to be independent predictors of day 28 mortality. Inclusion of estradiol levels further enhanced the ability of APACHE II scores to predict survival in patients with high mortality risk. A serum level of estradiol >40 pg/mL was also an independent predictor of concomitant AKI (p = 0.002) and correlated well with severity of renal dysfunction using RIFLE classification. Elevated serum estradiol levels also predicted the development of new AKI within 28 days of shock onset (p = 0.013). In conclusion, serum estradiol levels appear to have value in predicting 28-day mortality in septic shock patients. Increased serum estradiol levels are associated with higher severity of concomitant AKI and predict development of new AKI.