Background: Locus of control (LOC), individuals' perception that events occurring in life depend upon their own behavior and resources or not, has been shown to be associated with mental health disorders. However, few studies have considered the role of mental health prior to 2020 in this association. This study investigated the relationship between LOC and clinically significant symptoms of anxiety and/or depression during COVID-19 while controlling for preexisting clinically significant symptoms of anxiety and/or depression and psychoactive substance use. Methods: Online, self-report data were collected from the 2009 French TEMPO cohort. From March 2020 to May 2021, 904 individuals answered at least one of nine questionnaires aiming to better understand the consequences of the pandemic on mental health. The outcome was self-reported clinically significant symptoms of anxiety and/ or depression, and LOC was operationalized as a score. Generalized Estimating Equations models were used to account for repeated data. Results: We found a 30% odds decrease of experiencing clinically significant symptoms of anxiety and/or depression during COVID-19 for a 10-points increase of the LOC score (odds-ratio (OR)= 0.70; 95% CI=0.61-0.81), when adjusting for preexisting symptoms of anxiety and/or depression, loneliness, COVID-19 related stress and risky alcohol consumption. In other words, the higher the LOC score increases, the LOC becoming internal, the lower the anxiety and/or depression symptoms risk becomes. No interactions were found between LOC and other confounding factors. Limitations: LOC was assessed via the Internal Control Index, developed a few years ago. Conclusion: In a context of pandemic-related strains, this study provided an insight into the association between personality traits and internalized symptoms. The present results confirm the need for more Cognitive Behavior Therapies to help coping with mental health and feeling of lack of control.