Cystic fibrosis transmembrane conductance regulator (CFTR) is relevant to sperm quality, sperm capacitation and male fertility. However, it is still unknown whether CFTR can be a potential parameter for fecundity prediction in healthy couples. In this study, 135 healthy couples were divided into groups according to their fertility. We demonstrated that the sperm CFTR expression level of healthy males who never impregnated their partners (49 cases, 38.68 ± 2.71%) was significantly lower than that of fertile men (86 cases, 46.35 ± 2.32%). Sperm CFTR expression level accurately corresponded with fertility through the logistic regression model. Receiver operating characteristic (ROC) curve analysis showed that the cut-off value of sperm CFTR expression level for fecundity prediction was 43.75%. Furthermore, cumulative pregnancy rates (CPRs) of CFTR > 43.75% group and CFTR ≤ 43.75% group during the follow-up periods were 80.6% and 49.3% respectively. Meanwhile, the mean time to pregnancy (TTP) of CFTR ≤ 43.75% group (26.79 ± 2.35) was significantly longer than that of CFTR > 43.75% group (16.46 ± 2.42). Therefore, sperm CFTR expression level is relevant to fecundity of healthy couples and shows potential predictive capacity of fecundity.