Dairy goat kids are commonly disbudded in the United States without pain relief. Our objective was to identify an efficient pain management strategy by monitoring changes in plasma biomarkers and behavior of disbudded goat kids. A total of 42 kids (5-18 d old at the time of disbudding) were randomly allocated to 1 of 7 treatments (n = 6/treatment): sham treatment; 0.05 mg/kg i.m. xylazine (X); 4 mg/kg subcutaneous buffered lidocaine (L); 1 mg/kg oral meloxicam (M); xylazine and lidocaine (XL); xylazine and meloxicam (XM); and xylazine, meloxicam, and lidocaine together (XML). Treatments were administered 20 min before disbudding. One trained individual, blinded to treatment, disbudded all kids; sham-treated kids were handled similarly except the iron was cold. Jugular blood samples (3 mL) were obtained before (-20, -10, and -1 min) and after (1, 15, and 30 min, and 1, 2, 4, 6, 12, 24, 36, 48 h) disbudding and analyzed for cortisol and prostaglandin E2 (PGE2). Mechanical nociceptive threshold (MNT) testing was performed at 4, 12, 24, and 48 h after disbudding, and kids were weighed daily until 2 d post-disbudding. Vocalizations, tail flicks, and struggle behavior during disbudding were recorded. Cameras were mounted over home pens; continuous and scan observations over 12 periods of 10 min each, in the 48 h after disbudding, captured frequency of locomotion and pain-specific behaviors. Repeated measures and linear mixed models assessed treatment effects on outcome measures during and after disbudding. Models accounted for sex, breed, and age as random effects, and Bonferroni adjustments accounted for multiple comparisons. At 15 min after disbudding, XML kids had lower plasma cortisol concentrations compared with L (50.0 ± 13.2 vs. 132.8 ± 13.6 mmol/L) and M kids (50.0 ± 13.2 vs. 145.4 ± 15.7 mmol/L). Cortisol was also lower in XML kids over the first hour after disbudding compared with L kids (43.4 ± 9 vs. 80.2 ± 9 mmol/L). Change from baseline PGE2 was not affected by treatment. Behaviors observed during disbudding did not differ by treatment group. Treatment affected MNT such that M kids were more sensitive overall compared with sham kids (0.93 ± 0.11 kgf vs. 1.35 ± 0.12 kgf). None of the recorded post-disbudding behaviors were affected by treatment, but study activities did influence behavior over time, with kid activity levels declining in the first day after disbudding but largely recovering thereafter. We conclude that none of the drug combinations investigated here appeared to fully attenuate pain indicators during or after disbudding, but triple modality seems to have offered partial relief compared with some of the single-modality treatments.