Objectives were to determine effects of feeding pomegranate extract (POMx) rich in polyphenols on performance, health, nutrient digestion, and immunocompetence of calves in the first 70 d of age. Holstein calves (n = 67), at 2 ± 1 d of age (d 0 = birth day) were randomly assigned to 0 (control), 5 (POMx5), or 10. g/d (POMx10) of pomegranate extract containing 16.9% gallic acid equivalent (GAE) to result in intakes of 0, 850 and 1,700. mg of GAE/d or an average of approximately 0, 15, and 30. mg of GAE/kg of body weight (BW) per day. All calves received colostrum during the first 24. h, pasteurized milk thereafter until 61 d of age, and grain was fed ad libitum for the first 70 d of age. Calves were housed in individual hutches, and grain intake, attitude and fecal scores, incidence and duration of health disorders, and treatments for health problems were evaluated daily. Body weight was measured on 2 consecutive days at 2, 30, and 70 d of age and averaged for each measurement. Concentrations of glucose and 3-hydroxybutyrate were measured in plasma. Nutrient digestion was measured using total fecal collection during a 3-d period. Neutrophil phagocytic and killing activities and antibody response to immunization with ovalbumin were measured. Peripheral blood mononuclear cells were cultured and cytokine production measured. Feeding POMx had no effect on intake or BW gain in the first 30 d of age, but after 30 d of age, both grain dry matter intake and BW gain decreased with increasing addition of POMx, which resulted in calves that were 1.8 and 4.3. kg lighter at 70 d of age for POMx5 and POMx10, respectively, compared with controls. Feeding POMx did not influence dry matter, organic matter, or starch digestibility, but it reduced crude protein and fat digestion. Plasma concentrations of glucose and 3-hydroxybutyrate were similar among treatments throughout the first 70 d of age. Measures of calf health such as fecal and attitude scores, risk of fever, and rectal temperature were not altered by treatments. Similarly, neutrophil phagocytic and killing activities did not differ among treatments. On the contrary, feeding POMx increased synthesis of interferon-γ and interleukin-4 by peripheral blood mononuclear cells and improved total immunoglobulin G responses to ovalbumin vaccination. These results suggest that feeding POMx top-dressed onto the grain suppresses intake of grain and digestibility of fat and protein, likely because of the high tannin content. Nevertheless, polyphenols from POMx enhanced mitogen-induced cytokine production and response to vaccination, which might benefit immune competence of calves and potentially health. Additional studies are warranted to minimize the effect of POMx on intake and digestibility and to better understand the mechanisms by which polyphenols improve immune response of calves.