Aim: To investigate 3D morphology and biomarker profiles in a population of early onset TMJ Osteoarthritis (TMJ OA) subjects. Methods: Twelve subjects and controls underwent an exam and obtained a Cone beam CT (CBCT), as well as TMJ arthrocentesis and venipuncture. CBCT Datasets were used to construct 3D models of all condyles. Average OA and health models were created. 3D Shape Correspondence determined areas of statistically significant difference between models. Protein microarrays were used to analyze the synovial fluid (SF) and plasma samples. Shape Analysis MANCOVA was used to look for statistical correlations between biomarker levels and variations in surface morphology. Results: The average OA model demonstrated a smaller size with areas of statistically significant difference. 32 biomarkers were measured in the plasma and/or SF samples. Shape Analysis MANCOVA successfully mapped variations in 10 SF and 20 plasma biomarkers to specific regions of anatomic variability in the OA group.