Mitochondria are central to metabolism, nutrition and health but many factors can influence their efficiency. The objective of this study was to determine if mitochondrial enzyme activity rates of peripheral blood mononuclear cells (PBMCs) were affected by changes in blood composition, aging or breed. Data from 23 Holstein and 23 Jersey heifer calves was collected from age 4 to 66 d. Blood samples were collected at 1, 2 and 9 wk of age and analyzed using a Hemavet 950FS Hematology Analyzer (Drew Scientific, Miami Lakes, FL) to determine levels of neutrophils (NE, K/ul, %), lymphocytes (LY, K/ul, %), monocytes (MO, K/ul, %), eosinophils (EO, K/ul, %), and red cell distribution width (RDW, %). Additional blood was used to determine plasma total protein (TP, g/dl) and obtain crude mitochondrial extracts from the PBMC fraction using a mitochondria isolation kit from Abcam (Cambrige, MA). Enzyme activities for citrate synthase (CS), Complex I (CI), Complex IV (CIV) and Complex V (CV) were all determined using kits from Abcam (Cambrige, MA). Activity rates were compared by time point, breed, and blood parameters and were analyzed using the MIXED procedure of SAS (v.9.4) with repeated measures, breed as a fixed effect and time point as a random effect. Breed was not significant for all comparisons. CI activity was not different between time points but was affected by RDW (P < 0.02). CIV (P < 0.04) and CV (P < 0.01) showed an increase in activity with time point while CS (P < 0.01) decreased. An increase in EO and MO immune cell production increased CIV activity (P < 0.01) and CV activity (P < 0.01) respectively. As white blood cell (WBC) differential fluctuated CV activity increased as NE% (P < 0.01) and MO% (P < 0.01) decreased and LY% (P < 0.01) and EO% (P < 0.01) increased. These findings suggest that changes in mitochondrial enzyme activity is impacted by fluctuations in NE, LY, MO, EO cell populations and changes as calves age.