The investigation was undertaken to study some biochemical changes and cortisol levels in lameness among indigenous breeds of goats in Nigeria. Serum samples of 72 lame goats randomly selected were sampled from some villages in Ibadan, Oyo state, Nigeria. Analysis of the serum samples for biochemical parameters was estimated by commercially available standardized diagnostic kits. Glucose was analyzed using the spectrophotometry procedure. Cortisol level was estimated by Immuno chemiluminescence microparticle assay method using diagnostic products of IMMULITE diagnostic products corporation, Los Angles. Cross-bred goats possessed better values for most of the biochemical analytes, a significant difference was seen in ALT with a higher value of 14.5±3.54 in Cross-bred goats at (P<0.05). We found no significant difference in the male and female analytes, with the exception of AST, ALT, and GGT which have significant differences of higher values at (P<0.05) of 15.25±2.77, 12.06±2.02 and 8.69±2.21 respectively. There was a significant difference in the value of low-density lipoprotein with a higher value of 119.6±11.34 in the 2-21/2year age category. Severely affected lame goats had significant differences at (P<0.05) with higher values of some analytes as follows; K 3.4±0.37, Cl 100±3.54, HCO3 24.6±1.14, BUN 19.8±2.28, Creatinine 0.52±0.08, TP 6.48±0.15, Albumin 2.82±0.24. Cross-bred goats had the best value of 12.00±1.41 for cortisol. Male goats had the best cortisol value of 10.47±1.46. This study reveals the ruggedness and resilient ability of cross-bred goats, which shows that developing Nigerian indigenous breeds may be a viable option in preventing and managing lameness in Nigeria.