The dietary sodium-to-potassium ratio is positively correlated with blood pressure, and understanding this relationship is crucial for improving hypertension treatment. Moreover, few studies have examined these effects in both sexes. In this study, we aimed to investigate how supplementing (1.41% K+; HK) or depleting (DK) dietary potassium affects the development of salt-sensitive (SS) hypertension in male and female Dahl SS rats. Potassium supplementation attenuated blood pressure during 5 weeks of high salt (4% NaCl) diet in male but not in female rats. In contrast, potassium-deficient diet prevented the development of SS hypertension in both sexes, though this effect is unlikely to be protective. Both males and females on the DK diet were hypokalemic, had diminished heart rates, reduced weight gain, and females experienced high mortality. Males and females on the DK diet excreted less urinary sodium, but only females had elevated plasma sodium. Additionally, male and female DK-fed rats showed a decrease in multiple metabolites from the renin-angiotensin-aldosterone system. RNA-Sequencing of kidney cortical tissue revealed a number of genes that may underlie the sex-specific differences in phenotype. Analysis of renal ion channel and transporter expression revealed significant increases in basolateral inwardly rectifying potassium channels in DK rats. Male rats supplemented with potassium exhibited a decreased number and size of WNK4 puncta, whereas in potassium-supplemented females, there was no difference in puncta count and an increase in puncta size. Our data indicates there are sex-dependent differences in response to dietary potassium and that the distal nephron compensates for severe potassium deficiency.