Friedreich ataxia is caused by mutations in the frataxin gene, leading to neurodegeneration and premature death from cardiac dysfunction. Loss of frataxin impacts mitochondrial complex 1 (MC1) activity, suggesting MC1 may be a potential biomarker of frataxin levels and function. Biomarkers evaluated by noninvasive techniques are needed to monitor disease progression and treatment effects in people with Friedreich ataxia. Methods: PET with [(18)F]BCPP-EF, a ligand with high binding specificity for MC1, was used to measure cardiac and brain MC1 density in a mouse model of Friedreich ataxia and in healthy volunteers and participants with Friedreich ataxia. Results: An imaging protocol was developed in humans that included a 70-min brain scan immediately after administration of [(18)F]BCPP-EF followed by a 60-min cardiac scan 255 min after [(18)F]BCPP-EF administration. Cardiac [(18)F]BCPP-EF binding in participants with Friedreich ataxia was lower than that in healthy volunteers and in a mouse model of Friedreich ataxia versus wild-type mice (∼50% reduction in both). In the brain, no statistically significant difference in the [(18)F]BCPP-EF binding was detected between participants with Friedreich ataxia and healthy volunteers. Correlation analyses showed that blood frataxin and cardiac [(18)F]BCPP-EF levels decreased with increasing guanine-adenine-adenine expansion size (R = -0.82 and -0.78, respectively; both P < 0.05) but not in the precentral gyrus (R = 0.63; P < 0.05). Conclusion: MC1 density as measured using [(18)F]BCPP-EF-based PET may be a viable biomarker of mitochondrial deficit and frataxin levels in people with Friedreich ataxia.