Phytonutrients exhibit both ruminal and post-ruminal effects in ruminants and there may be additive effects on performance when phytonutrients are combined with other rumen modifiers such as ionophores. The objective of this experiment was to investigate the effects of phytonutrients alone or in combination with monensin on productivity, blood cells, and fat mobilization in lactating dairy cows. Thirty-six Holstein cows (average days in milk, 120 ± 23.1 d; average body weight, 676 ± 75.8 kg) were used in a 9-wk randomized complete block design study. Cows were blocked in blocks of 3 based on days in milk, milk yield, and parity following a 2-wk covariate period. Cows within a block were randomly assigned to one of the following treatments (12 cows/treatment): 450 mg/cow/d monensin (MO), 1,000 mg/cow/d of a mixture of cinnamaldehyde, eugenol, and capsicum (XT), and 250 mg/cow/d of a product containing capsicum oleoresin in addition to MO (MOCAP). Cows were housed in a free-stall barn equipped with Calan Feeding System for monitoring individual feed intake and fed ad libitum once daily. Treatments were top-dressed at the time of feeding. Dry matter intake and milk yield were not affected (P ≥ 0.18) by treatments (average 31.0 and 47.4 kg/d; SEM = 0.52 and 0.81, respectively). Compared with MO, XT increased (P = 0.04) feed efficiency (1.48 and 1.58 kg/kg, respectively). Concentrations of milk fat, true protein, and lactose were similar (P ≥ 0.46) among treatments. The expression of hormone-sensitive lipase in adipose tissues tended to increase (P = 0.09) for MOCAP compared with MO. However, blood nonesterified fatty acids were not affected (P = 0.26) by MOCAP. Treatments had no effect (P ≥ 0.15) on blood urea nitrogen, red blood cells, and white blood cells except a slight decrease (P = 0.10) in monocyte counts for XT. Relative to monensin, phytonutrients had no or subtle effect on feed intake, milk yield and composition, blood cells, and fat mobilization in dairy cows. However, a mixture of cinnamaldehyde, eugenol, and capsicum increased feed efficiency compared with monensin.