Activated immune cells avidly utilize glucose and are insulin sensitive. Chromium (Cr) increases insulin sensitivity and thereby may affect immune function. Objectives were to evaluate supplemental Cr (KemTRACE Chromium 0.04%, Kemin Industries Inc., Des Moines, IA) effects on circulating metabolites and leukocytes following an i.v. lipopolysaccharide (LPS) challenge in lactating 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). Cows received experimental diets throughout the trial. After acclimation (3 d) baseline values were obtained during period 1 (3 d). 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. Circulating NEFA in PF cows increased (95%) from 6 to 18 h post-bolus while LPS cows increased from 12 to 18 h (63%); thereafter, NEFA decreased in all treatments (P < 0.01). Circulating BUN was increased in LPS vs. PF cows throughout P2 (31%; P = 0.02). Circulating β-hydroxybutyrate tended to decrease in LPS vs. PF cows (16%; P = 0.07) and increased in all cows throughout the 2 d (P < 0.01). Relative to PF cows, circulating LPS-binding protein and serum amyloid A in LPS cows increased 2 and 5-fold, respectively (P < 0.01). Overall, Cr-supplemented cows had increased (22%; P = 0.03) monocytes. Relative to PF cows, WBC and neutrophil counts in LPS cows initially decreased, then progressively increased 58 and 163%, respectively (P < 0.01). Between 12 and 48 h post-bolus, neutrophils increased (12%; P = 0.04) in LPS-Cr vs. LPS-CON cows. In summary, Cr increased the neutrophil response following an LPS challenge, but had minimal effects on circulating energetic metabolites.