The aim of this study was to evaluate the effect of a single dose of subcutaneous (s.c.) meloxicam administered at the time of knife and band castration on inflammatory response and wound healing over 56-d post-castration. Seventy-two Angus crossbred calves (47.3 ± 6.70 kg of body weight [BW] and 7 to 8 d of age) were randomly assigned according to a 3 × 2 factorial design assessing castration method: sham (CT), band (BA), and knife (KN) castration, and pain mitigation: non-medicated (NM) and medicated calves (M) injected s.c. with meloxicam (0.5 mg/kg of BW). Calf BW, rectal temperature, swelling ("0": no swelling; "4": swelling needing intervention) and healing score ("1" to "5" with "5" being completely healed), scrotal circumference, and maximum scrotal temperature were measured on d -1, immediately before castration (d 0), and weekly thereafter over a 56-d period. Blood samples for haptoglobin (Hp), serum amyloid-A (SAA), and complete blood cell count were collected according to the same schedule. Hair samples were collected on d -1, 28, and 56 to determine cortisol concentrations. Standing and lying behaviors were measured using accelerometers that were placed on the calves on d -1 until d 35, and visual observations of behaviors related to pain were recorded once a week for 35 d. Knife-castrated calves achieved swelling scores of "3" and "2" between d 7 and 14, which was sooner (Z< 0.05) than in BA calves (from d 14 to 35). In addition, greater (P = 0.03) concentrations of SAA were observed in BA calves (76.9 ± 0.12 g/liter) compared with CT (57.6 ± 0.12 g/liter) and KN (51.6 ± 0.12 g/liter) from d 7 to 35. Healing scores of "2" and "4" tended to be achieved sooner (Z < 0.10) in KN calves than in BA calves, although healing scores of "3" tended to be achieved sooner (Z < 0.10) in BA calves than KN calves. No differences (P > 0.10) were observed among treatments for hair cortisol on d -1 and 28, but on d 56, hair cortisol concentrations in BA-NM calves were greater (P > 0.05) than for CT-NM, BA-M, KN-NM, and KN-M, and tended to be greater (P = 0.08) than for CT-M calves. Lying duration tended (P = 0.10) to be greater and suckling behavior tended (P = 0.08) to be lower in NM than M calves. A single s.c. injection of meloxicam did not reduce long-term inflammatory responses or improve wound healing; however, it may be useful in reducing pain and stress in band castrated calves as evidenced by reduced hair cortisol concentrations up to 56 d post-castration.