The objective was to determine the influence of breed and planes of preweaned milk replacer (MR) nutrition on the immune responses of pre- and postweaned dairy calves. Forty-two bull calves (n = 20 Holstein and n = 22 Jersey, 2. ±. 1. d old) were studied. Holstein and Jersey calves came from separate dairies. Calves were fed either a higher plane of MR nutrition or a lower plane of MR nutrition. Holstein and Jersey calves on the lower planes of MR nutrition were fed 454. g (as fed)/d of a 20% crude protein (CP)/20% fat MR. Holstein calves on the higher plane of MR nutrition were fed 810 and 1,180. g (as fed)/d of a 28% CP/20% fat MR for wk 1 and wk 2 to 6, respectively. Jersey calves on the higher plane of nutrition were fed 568 and 680. g (as fed)/d of a 28% CP/25% fat MR for wk 1 and wk 2 to 6, respectively. On d 4, 42, and 77, peripheral blood was collected for ex vivo immunological analyses, and on d 7 all calves were challenged subcutaneously with commercially available lipopolysaccharide (LPS) from Escherichia coli (4. μg/kg of body weight); clinical and biochemical responses were evaluated at 0, 1, 2, 3, 4, 5, 6, 9, 12, 24, and 72. h. We observed a breed difference in total serum protein, wherein Jersey calves had higher concentrations than Holsteins. Holsteins and calves fed the higher plane of MR nutrition had greater glucose concentrations following the LPS challenge. With the exception of plasma haptoglobin concentrations at 24. h postchallenge, we observed no treatment × time interactions following the LPS challenge. Calves fed higher planes of MR nutrition had greater plasma haptoglobin concentrations 24. h following the LPS challenge. Isolated mononuclear cells from Holstein calves secreted more tumor necrosis factor-α than did cells from Jersey calves when stimulated ex vivo with LPS on d 77. In addition, when whole blood was incubated with a live enteropathogenic E. coli culture, blood from Holsteins had a greater killing capacity than did whole blood from Jerseys. Calves fed higher planes of MR nutrition had greater neutrophil oxidative burst intensities at d 77 when cocultured with E. coli for 10. min. In addition, Jersey calves fed the lower plane of MR nutrition had reduced neutrophil oxidative burst capacity and whole blood E. coli killing at d 77 compared with the other groups. These data indicate that Jersey calves had lower measures of many innate immune variables despite likely having greater passive transfer, as evidenced by greater total serum protein concentrations. Furthermore, feeding a higher plane of MR nutrition to Jersey calves improved some postweaning innate immune responses.