Factors underlying biological differences in feed efficiency were investigated in order to determine if these factors could be utilized as indirect measures of feed efficiency. Residual feed intake (RFI) was determined in 36 beef heifers. Hourly blood samples were taken over 24 hours at 367 ± 15 days, 542 ± 23 days, and 704 ± 25 days of age corresponding to open, early pregnancy, and late pregnancy, respectively. Then hematological measures of basic metabolic processes that contribute significantly to energy expenditures were determined including albumin, urea, creatine kinase, glutamate dehydrogenase, aspartate aminotransferase and carbon dioxide. Creatine kinase, aspartate aminotransferase and carbon dioxide showed relationships with RFI in open heifers, urea and creatine kinase in late gestation and carbon dioxide overall. These associations tend to be reflective of differences in liver function, tissue turnover and whole body metabolism that may act as effective indirect measures of RFI.