The mechanisms of salt-sensitive (SS) hypertension are complex and far from clear. Available medications are insufficient to control blood pressure (BP) in the SS subjects, and there is a need for the development of novel effective therapies. SS hypertension is accompanied with an early onset of proteinuria, which results from the loss of podocytes. Many reports highlight that in this disease ultrastructural abnormalities and deficient metabolism in the renal mitochondria may precede histological injury. We hypothesized that podocyte damage occurs in part due to mitochondria dysfunction. Dahl SS rats were used here as an established animal model of SS hypertension. All rats were fed a 0.4% NaCl (normal salt, NS) diet until 8 weeks of age when they were challenged with a high salt (HS) 4% NaCl diet for 21 days. At the end of the protocol BP was measured, kidneys were cleared from blood, tissues were collected, and cortical glomeruli were isolated and subjected to imaging, WB and other applications. Systolic BP was elevated in the HS diet fed rats (171±9 vs 148±6 mmHg in HS vs NS diet fed rats). HS diet fed rats exhibited renal lesions, kidney hypertrophy, decreased GFR and exacerbated glomeruli damage compared to the NS group. We did not observe changes in the renal cortical expression of PGC1α; cortical mtDNA content (ND1 and ND6 gene expression vs genomic DNA) was not affected by a HS diet. Seahorse assay performed on freshly isolated glomeruli revealed that basal mitochondria respiration, maximal respiration, and spare respiratory capacity were lower in the HS group (28 ± 14%, 47 ± 15% and 37 ± 9% lower, respectively, vs NS group). No difference was observed in ATP production, or mitochondrial Complex V (ATPase) activity (expressed as oxidation rate of NADH and measured in glomerular pellets). Using confocal imaging and mitoPY1 staining we detected higher baseline H 2 O 2 level, lower antioxidant capacity, and fragmented mitochondria in the podocytes of the glomeruli isolated from HS diet fed group. EM analysis showed that HS mitochondria have structural abnormalities (swelling, enlargement, less defined cristae, and reduced number). We conclude that glomerular mitochondria in SS hypertension are functionally and structurally impaired.