End-stage kidney disease (ESKD), the most advanced stage of chronic kidney disease (CKD), requires renal replacement therapy or kidney transplant to sustain life. To accomplish durable dialysis access, the creation of an arteriovenous fistula (AVF) has emerged as a preferred approach. Unfortunately, a significant proportion of patients that receive an AVF experience some form of hand dysfunction, however the mechanisms underlying these side effects are not understood. In this study, we utilized nuclear magnetic resonance (NMR) spectroscopy to investigate the muscle metabolome following iliac AVF placement in mice with CKD. To induce CKD, C57BL6J mice we fed an adenine-supplemented diet for three weeks and then randomized to receive AVF or Sham surgery. Two-weeks following surgery, the quadriceps muscles were rapidly dissected and snap frozen for metabolite extraction and subsequent NMR analysis. Principal component analysis demonstrated clear separation between groups, confirming a unique metabolome in mice that received an AVF. AVF creation resulted in reduced levels creatine, ATP, ADP, as well as increased levels of IMP and several tricarboxylic acid cycle metabolites suggesting profound energetic stress. Pearson correlation and multiple linear regression analyses identified several metabolites that were strongly linked to measures of limb function (grip strength, gait speed, mitochondrial respiration). In summary, AVF creation generates a unique metabolome profile in the distal skeletal muscle indicative of an energetic crisis and myosteatosis.