This experiment investigated the link between production class and inflammation in mid-lactation Holstein cows with or without clinical mastitis. Forty cows were sampled, 20 positive for clinical mastitis and 20 healthy control cows. Within the mastitis and healthy groups, cows were further classified by level of milk production (Low = 23 to 25 kg/d vs. High = 28 to 35 kg/d). Therefore the experimental design was a 2 × 2 factorial with health status and level of milk production as the main effects (n = 10 cows per health status x level of milk production). All cows were sampled from a single commercial dairy farm with 1200 lactating Holstein cows with an average milk yield of 28 kg/d. Sampled cows were 80 to 120 DIM in their 2nd or 3rd parity. A positive mastitis case was defined as clinical signs and a positive California mastitis test. Cows had ad libitum access to feed and water. A peripheral blood sample was collected from each cow and analyzed for plasma haptoglobin concentrations. Among the healthy cows, plasma haptoglobin concentrations were greater for the high production group compared with the low production group (132 ± 12.9 vs. 93 ± 23.0 μg/mL; P ≤ 0.05). Although cows with mastitis had greater plasma haptoglobin concentrations compared with the healthy cows, there was no difference (P = 0.71) between the low and high milk production groups for cows with clinical mastitis (1,193 ± 238 vs. 1,145 ± 211 μg/mL, high and low, respectively). These data indicate that increased milk production among healthy Holstein cows may cause an increase in low level inflammation when compared with cows that produced less milk. The mild increase in plasma haptoglobin concentrations may be associated with a greater intake of certain nutrients and/or overall metabolic activity. Clinical mastitis caused a large increase in plasma haptoglobin concentrations that was independent of milk production class.