Alveolar fluid clearance mediates perinatal lung transition to air breathing in newborn infants, which is accomplished by epithelial Na channels (ENaC) and Na-K-ATPase. Male sex represents a major risk factor for developing respiratory distress, especially in preterm infants. We previously showed that male sex is associated with reduced epithelial Na transport, possibly contributing to the sexual dimorphism in newborn respiratory distress. This study aimed to determine sex-specific effects of sex steroids on epithelial Na transport. The effects of testosterone, 5α-dihydrotestosterone (DHT), estradiol, and progesterone on Na transport and Na channel expression were determined in fetal distal lung epithelial (FDLE) cells of male and female rat fetuses by Ussing chamber and mRNA expression analyses. DHT showed a minor effect only in male FDLE cells by decreasing epithelial Na transport. However, flutamide, an androgen receptor antagonist, did not abolish the gender imbalance, and testosterone lacked any effect on Na transport in male and female FDLE cells. In contrast, estradiol and progesterone increased Na transport and Na channel expression especially in females, and prevented the inhibiting effect of DHT in males. Estrogen receptor inhibition decreased Na channel expression and eliminated the sex differences. In conclusion, female sex steroids stimulate Na transport especially in females and prevent the inhibitory effect of DHT in males. The ineffectiveness of testosterone suggests that Na transport is largely unaffected by androgens. Thus, the higher responsiveness of female cells to female sex steroids explains the higher Na transport activity, possibly leading to a functional advantage in females.