The objective of this study was to evaluate the effects of early life fecal microbiota transplantation (FMT) on health and performance of neonatal dairy calves. The adult donor was selected based on health and production records as well as fecal samples testing negative for infectious pathogens. Sixteen healthy newborn Holstein calves (n = 8/trt) were used in a completely randomized design and housed in individual hutches from birth to 7 wk of age. Calves were fed 2.8 L/d of antibiotic-free milk replacer 2 × /d during wk 1 to 5, 1 × /d on wk 6, and weaned at wk 7. Antibiotic-free starter and water were fed ad libitum. Calves were assigned to either a baseline nutritional program (CON) or 1 × /d inoculations with 25 g of fecal donor material (FMT) mixed in the milk replacer from 8 to 12 d of age. Blood samples were collected weekly for immunometabolic profiling and polymorphonuclear leukocytes (PMNL) isolation for gene expression analysis. Data were analyzed using the MIXED procedure of SAS, where treatment, wk, and their interaction were the fixed effects in the model, and calf the random effect. Orthogonal contrasts were used to determine linear and quadratic effects over time. There was a trend (P = 0.09) for greater BW (50.8 vs 52.7 ± 0.7 kg) in FMT calves. A TRT × Wk (P = 0.02) was observed in haptoglobin, that was reflected in a positive quadratic effect (P = 0.04) in FMT calves but not in CON. Similarly, a TRT × Wk (P = 0.07) in IL1B resulted in a positive quadratic effect (P = 0.07) over time in FMT, and a linear increase (P = 0.07) in CON. A trend for a TRT × Wk (P = 0.06) was observed in the liver function biomarker paraoxonase, which resulted in greater (P < 0.01) paraoxonase in FMT calves than CON at 3 wk of age. The TRT × Wk (P = 0.09) in NFKB1 mRNA expression in PMNL was associated with a greater (P = 0.03) expression in FMT calves at wk 1 (or 7 d) before the FMT was performed, but NFKB1 expression was similar between FMT and CON at wk 2 and 3. These results suggest that early life FMT in neonatal calves have positive effects in their neonatal stage not only on growth performance but also in mediating the inflammatory response and liver function.