Objective To evaluate the impact of COVID-19 pandemic exposure on changes in alcohol use and mood from years 1 to 2 after traumatic brain injury (TBI). Methods We used a difference-in-difference (DiD) study design to analyze data from 1,059 individuals with moderate-to-severe TBI enrolled in the TBI Model Systems (TBIMS) National Database. We defined COVID-19 pandemic exposure as participants who received their year 1 post-injury interviews prior to January 1, 2020, and their year 2 interview between April 1, 2020 and January 15, 2021. Pandemic-unexposed participants had both year 1 and 2 follow-up interviews before January 1, 2020. We measured current alcohol use as any past month alcohol use, average number of drinks per drinking occasion, and past month binge drinking. We measured depression symptoms using Patient Health Questionnaire-9, and anxiety symptoms using the Generalized Anxiety Disorder-7. Results We found persons with TBI exposed to the pandemic had greater increases in the average number of drinks per occasion from year 1 to 2 post-injury compared to pandemic-unexposed individuals (β = 0.36, 95% CI: 0.16, 0.57, p = 0.001), with males, adults <65 years old, and Black and Hispanic subgroups showing the greatest increases in consumption. Though average consumption was elevated, changes in rates of any alcohol use or binge drinking by pandemic exposure were not observed. Overall, there were no significant changes in depressive and anxiety symptoms over time between pandemic exposed and unexposed groups; however, pandemic-exposed Hispanics with TBI reported significant increases in anxiety symptoms from year-1 to year-2 post-injury compared to pandemic-unexposed Hispanics (β = 2.35, 95% CI: 0.25, 4.47, p = 0.028). Conclusion Among persons living with TBI, those exposed to the pandemic had significant increases in average alcohol consumption. Pandemic-exposed Hispanics with TBI had large elevations in anxiety symptoms, perhaps reflecting health inequities exacerbated by the pandemic, and suggesting a need for targeted monitoring of psychosocial distress.