Exogenous fibrolytic enzymes have been used to improve feed efficiency by releasing nutrients bound in complex feed matrices such as hemicellulose. β-Mannanase, an exogenous fibrolytic enzyme, is known to hydrolyze mannan structures found in plant hemicellulose matrices. β-Mannanase acts in 3 main ways; reduction of feed viscosity, improvement of energy metabolism, and decreased immune stimulation. Objectives of this study were to determine the effects of β-mannanase supplementation on immunological and metabolic responses in lactating dairy cows. Two weeks after calving, 20 Holstein cows (10 multiparous and 10 primiparous), were blocked by parity and assigned to one of 2 diets for 182 d. All cows were housed in the same environment and fed the same basal diet. The basal diet of the treatment group was supplemented with β-mannanase (CTCzyme) at 0.1% of concentrate DM. Haptoglobin (Hp), Immunoglobulin G (IgG) and somatic cell counts (SCC) were analyzed for immune responses and nonesterified fatty acids (NEFA) were analyzed to explore metabolic responses. Blood samples were taken once weekly, starting 14 d after calving, and were analyzed for immune and metabolic markers. Milk samples were collected twice daily and analyzed separately for SCC. There was a significant reduction in Hp levels (P = 0.01) in supplemented multiparous cows, compared with control multiparous cows, indicating that β-mannanase was associated with decreased systemic inflammation. Primiparous cows fed β-mannanase showed tendencies for reduced Hp levels (P = 0.06), when compared with control primiparous cows. Multiparous cows are considered to be more susceptible to acute infections and inflammation, so the enzyme may have a better effect in multiparous cows. NEFA levels tended to be lower in cows fed β-mannanase (P = 0.08), regardless of parity, suggesting that β-mannanase was associated with improved energy balance during early to mid-lactation. IgG and SCC were not affected by β-mannanase supplementation, regardless of parity. Results suggest supplementation of β-mannanase could aid in reduced instances of metritis and mastitis, through reduced systemic inflammation, and improved energy balance in lactating cows.