The objective of this experiment was to determine how source of supplementary selenium (Se) affects animal performance during an intramammary endotoxin challenge. Twenty mid-lactation multiparous Holstein cows (591 ± 46 kg BW) were blocked by days in milk (157 ± 17 DIM) and randomly assigned to 1 of 2 treatments: 1) 0.30 ppm (100% NRC requirements on a dry matter basis) of supplementary organic (selenized yeast) Se premix, or; 2) 0.30 ppm of supplementary inorganic (sodium selenite) Se premix, top dressed and mixed into a basal ration that was fed once daily. Dry matter intake (DMI) and milk production were recorded daily. Following a 75-d dietary adaptation period, cows received an intramammary infusion of 50 μg of lipopolysaccharides (LPS; Escherichia coli strain O111:B4) diluted in 10 mL of sterile saline in one front quarter. Rectal temperatures were recorded at −1.5, 0, 2, 4, 6, 8, 10, 12, 24, and 48 h. Data were analyzed using PROC GLIMMIX in SAS. Statistical models included the fixed effects of treatment, time, and their interaction, and the random effects of block and cow nested within treatment. During the adaptation period, average daily DMI (23.54 ± 0.483 kg) and milk production (34.97 ± 1.730 kg) were not different (P > 0.05) between treatments. Results revealed no treatment differences in daily milk production and DMI during the LPS challenge, although there was a time effect for all parameters (P < 0.001). There was a tendency (P = 0.07) for inorganic cows to have higher DMI in the 12 h following LPS infusions. Cows experienced a significant (P < 0.001) change in body temperature during the day of LPS infusions, with a peak temperature occurring 6 h following infusions (40.59 ± 0.107°C), with no differences between treatments. These results indicate that animal performance during immune challenge is minimally affected by source of supplementary Se. Further analysis is required to determine antioxidant capacity and oxidative stress in cows supplemented with differing sources of Se.