Immunostimulation partitions nutrients away from productive processes. Chromium (Cr) improves insulin sensitivity and may ameliorate the energetic cost associated with activated immune cells; thus improving animal production and welfare. Objectives were to evaluate the effects of dietary Cr (KemTRACE Chromium 0.04%, Kemin Industries Inc., Des Moines, IA) on immune system glucose utilization and production parameters following an i.v. lipopolysaccharide (LPS) challenge in non-pregnant lactating Holstein cows. Cows were enrolled in a 2x2 factorial design and assigned to 1 of 4 treatments: 1) pair-fed (PF) and control (PF-CON; 5 mL saline; n = 5), 2) PF and Cr (PF-Cr; 5 mL saline; n = 5), 3) LPS-euglycemic clamp and control (LPS-CON; 0.375 μg/kg BW LPS; n = 5), and 4) LPS-euglycemic clamp and Cr (LPS-Cr; 0.375 μg/kg BW LPS; n = 5). During period 1 (3 d), cows received their respective dietary treatments and baseline values were obtained. At the initiation of period 2 (2 d), a 12 h LPS-euglycemic clamp was conducted or cows were PF to their respective dietary counterparts. LPS infused cows experienced mild hyperthermia (+0.82°C) for the first 6 h postbolus, while body temperature of PF treatments remained unchanged (P < 0.01). Relative to PF cows, infusing LPS decreased milk yield (58%; P < 0.01) and this was not influenced by Cr supplementation. Administering LPS decreased DMI (40%) relative to baseline during P2, and was similar to PF cows by experimental design (P > 0.35). Despite marked hypophagia, circulating insulin increased 9 and 15-fold in LPS infused cows at 6 and 12 h postbolus, respectively, relative to PF cows (P < 0.01). Compared with LPS-CON, LPS-Cr cows had decreased insulin 6 h postbolus (48%; P < 0.05). The total glucose deficit accumulated over 12 h, as determined by LPS-euglycemic clamp and reduced milk yield, was 120, 319, 1772, and 1781 g for PF-CON, PF-Cr, LPS-CON, and LPS-Cr treatments, respectively but was not influenced by Cr. In summary, Cr ameliorated LPS-induced hyperinsulinemia, but did not alter glucose dynamics in the 2 d following a severe immune challenge.