Osteoarthritis is a major cause of chronic lameness in Asian elephants (Elephas maximus) in captivity worldwide. Radiology and other imaging technologies are of limited use in the early diagnosis of this condition in elephants. Collagen II is a major component of articular cartilage. The degradation and formation of collagen II can be monitored by the measurement of specific biomarkers in biologic fluids such as serum. It is possible that these biomarkers could also prove useful in identifying disease in elephants. In this study two commercially available immunoassays which measure a marker of collagen II degradation (C2C) and a marker of collagen II formation (CPII) were evaluated in Asian elephants. The ability of the assays to detect and measure C2C and CPII in the serum of Asian elephants was confirmed. Median serum concentration of C2C was 148 ng/L in nonlame elephants (n = 33) and 91.2 ng/L in lame elephants (n = 7). The difference was statistically significant (P = 0.0002). Median serum concentration of CPII was 519.3 ng/L in nonlame elephants and 318.7 ng/L in lame elephants. The difference was also statistically significant (P = 0.039). Whereas CPII concentrations in lame elephants mirrored findings from human and animal osteoarthritis studies, C2C concentrations did not. Further studies which evaluate these and other similar biomarkers are necessary to elucidate their usefulness in the diagnosis of osteoarthritis in proboscidae.