Renal K⁺ retention is activated during pregnancy through a mechanism unknown to date. Here, we showed that the renal stimulation of H,K-ATPase type 2 (HKA2), whose expression was recently identified to be progesterone-dependent, is part of the mechanism favoring K⁺ accumulation during gestation. Moreover, investigation of the gestational phenotype of HKA2-null mice compared to their wild-type (WT) littermate revealed a decrease in fertility (gestation was successful in 33 % of HKA2-null mice vs. 83 % of WT mice) and in litter size (6.5 ± 0.6 and 7.8 ± 0.4 fetuses per litter, respectively). We also observed that urinary K⁺ excretion decreased by 20 % and plasma K⁺ concentration rose slightly (11 %) in WT mice during gestation (relative to basal conditions). In contrast, the renal excretion of K⁺ and plasma K⁺ levels in HKA2-null mice remained constant during gestation, whereas fecal K⁺ excretion increased. As a consequence, HKA2-null mice did not accumulate K⁺ in their extracellular compartment as efficiently as WT mice did. Finally, the link between inefficient K⁺ balance adaptations and gestational complications was established when we observed that these complications could be reversed with an increased K⁺ uptake. Altogether, these results define a novel physiological role for the HKA2 transporter and uncover a link between K⁺ metabolism and fertility.