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 (PBMC) changed over time and were influenced by shifts in blood composition, average daily gain, or breed. Data from 22 Holstein and 18 Jersey heifer calves was collected from age 4 to 301 d. Blood samples were collected at 1, 2, 9 and 36 wk of age and analyzed using a Hemavet 950FS Hematology Analyzer (Drew Scientific, Miami Lakes, FL) to determine blood composition and health status. 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. Time point significantly affected activity in all complexes (P < 0.01) but breed was not different (P > 0.1). Animals with greater complex I activity showed increased pre-wean ADG (P < 0.01) and animals with lower citrate synthase activity tended to have increased 36 wk ADG (P < 0.1). CS, CI, and CV showed a reduction in activity from 1 to 36 wk (P < 0.001). Activity of CS unexpectedly peaked at 2 wk (P < 0.001) plausibly resulting from the increase of scours onset during this time point. These findings suggest that changes in mitochondrial enzyme activity occur as calves age and grow and may be affected by an immune challenge such as scours onset.