The evidence overwhelming suggests that the COVID-19 pandemic, its associated public health measures, and the consequences of these measures negatively affected the mental health and well-being of post-secondary students; however, few studies have examined which subsects of this population were most adversely affected on a global scale. This study sought to identify which subsets of post-secondary student populations were most impacted by COVID-19-related public health measures. Data from a large global survey was used to identify levels of stress and quality of life. These data were assessed against demographic variables to identify correlational relationships and odds-ratios. Results highlighted that students who identified as being from a low-income family, having special needs or living with a non-COVID health issues, and/or self-reported as female or other gender, reported higher increases in stress and greater decreases in quality of life. The implications of these findings suggest that post-secondary institutions can proactively identify at-risk students and support them through these challenges. Such practices may reduce the negative impacts that adversities have on stress levels and quality of life of these populations, and mitigate the negative consequences associated with decreased mental health and well-being.