Introduction: The clinical criteria for Traumatic encephalopathy syndrome (ccTES) were developed to improve the diagnosis of Chronic traumatic encephalopathy (CTE). This study aimed to determine whether there was an association between a clinical diagnosis of Traumatic encephalopathy syndrome (TES) and changes in serum biomarkers, balance, neuroimaging, and cognition among athletes in the Professional Athletes Brain Health Study (PABHS).Methods: Of the cohort, 130 professional fighters met age or retirement criteria and went to a consensus conference, with 52 fighters (40%) meeting the criteria for TES. A generalized linear model with generalized estimating equations was utilized to assess the odds of disease for balance and serum biomarker outcomes, while multiple linear regression models compared MRI regional brain volumes and cognitive performance between TES+ and TES- groups. Results: At a threshold of 15 professional fights, significantly greater odds of disease were present for every unit increase in serum GFAP. Likewise, the odds of a TES diagnosis significantly increased by 3% with every additional professional fight completed. A significant association was observed between the presence of a TES diagnosis and worsening performance on single-leg and tandem balance assessments. Significant total mean differences were found in all MRI volumetric regions of interest among TES+ compared to TES-. The rate of volumetric change significantly increased for lateral and inferior lateral ventricles and decreased for the hippocampus, subcortical gray matter, total gray matter, and posterior corpus callosum. Conclusion: The 2021 ccTES distinguishes group differences in the longitudinal presentation and odds of disease for serum biomarkers, balance assessments, regional volumetric loss, and cognitive decline among professional fighters 35 years of age and older. This study indicates a TES diagnosis may be useful in professional sports, further suggesting the application of the ccTES may be valuable clinically in predicting cognitive and functional decline.