We have previously demonstrated that the circadian clock protein Per1 coordinately regulates multiple genes involved in sodium reabsorption in renal collecting duct cells. Consistent with these results, Per1 KO mice exhibit dramatically lower blood pressure than WT mice. The proximal tubule is responsible for a majority of sodium reabsorption. Previous work has demonstrated that expression of the sodium hydrogen exchanger NHE3 oscillates with a circadian pattern and SGLT1 has been demonstrated to be a circadian target in the colon, but whether these target genes are regulated by Per1 has not been investigated in the kidney. The goal of this study was to determine if Per1 regulates the expression of NHE3, SGLT1, and SGLT2 in the kidney. Pharmacological blockade of nuclear Per1 entry resulted in decreased mRNA expression of SGLT1 and NHE3, but not SGLT2 in the renal cortex of mice. Per1 siRNA and pharmacological blockade of Per1 nuclear entry in human proximal tubule HK-2 cells yielded the same results. Examination of heterogeneous nuclear RNA (hnRNA) suggested that the effects of Per1 on NHE3 and Sglt1 expression occurred at the level of transcription. Chromatin-immunoprecipitation experiments demonstrated the interaction of Per1 and the circadian protein CLOCK with the promoters of NHE3 and SGLT1. These interactions were reduced by blockade of Per1 nuclear entry. Importantly, both membrane and intracellular protein levels of NHE3 and SGLT1 were decreased following blockade of nuclear Per1 entry. These data demonstrate a role for Per1 in the transcriptional regulation of NHE3 and SGLT1 in the kidney.