The objective of this study was to determine the diagnostic ability of serum amyloid A (SAA) and fibrinogen for early detection of surgical site infection (SSI) after equine internal fixation. Horses undergoing internal fixation for fracture, arthrodesis, or osteotomy with internal fixation for limb deformity were included in the study. SAA and fibrinogen were measured on blood samples preoperatively and on days 1, 3, 5, 7, 10, and 14 postoperatively. Statistical analysis included use of Spearman's rank correlation, logistic regression, and calculating the area under the receiver operating characteristic (ROC) curve. SAA and fibrinogen measurements were both associated with SSI, with SAA being considered an excellent marker (area under the ROC curve 0.8) and fibrinogen being considered acceptable (<0.8). As the amount of time postoperatively increased, SAA elevations indicated a higher likelihood of SSI (area under the ROC curve 0.8 compared with fibrinogen 0.7). SAA and fibrinogen were predictive markers of SSI and SAA is of greater diagnostic utility when compared with fibrinogen. Persistent elevations of SAA postoperatively are associated with the development of SSI. Serial monitoring of SAA can be used to help predict the development of SSI in horses undergoing internal fixation. This may lead to earlier suspicion, and therefore recognition and treatment of SSI.