The autosomal genes mitochondrial transcription factor A (TFAM) and uncoupling protein 2 (UCP2) are both involved in moderating mitochondrial energy production. This study investigated single nucleotide polymorphisms (SNPs) in TFAM and UCP2 and their associations with growth, fertility, milk production and survival in UK dairy cows. Holstein–Friesian heifers (n = 509) were recruited at birth and monitored until they either reached the end of their second lactation or were culled. Weight, height, length and girth were measured at 1, 6 and 15 months of age to assess growth. Fertility records were obtained for both heifers and cows and production traits (milk per day, peak yield and 305-day yield) were recorded in the first and second lactation. Mixed model and survival analyses revealed that TFAM3 GG homozygotes, representing 49% of the population, were larger than the AG heterozygotes throughout the growing period, had worse fertility, produced less milk in both lactations and were more likely to be culled. TFAM3 AA homozygotes (7% of population) were generally smaller as heifers, had slightly worse fertility and also produced less milk. This suggests a clear advantage for maximizing the heterozygotic population for this SNP. Furthermore, the results for milk per day suggest an overdominant effect, as both homozygotes of TFAM3 had significantly lower yields than the heterozygote. For UCP2, the minority CG heterozygotes (6% of population) were larger as heifers, had a reduced age at first conception and a delayed return to cyclicity after calving, when compared against the majority (94%) GG homozygotes.