Many individuals have experienced increased stress and distress during the COVID-19 pandemic. College students with disabilities may have experienced the pandemic as more threatening and stressful due to exposure to risk factors for contracting COVID-19 and stressors related to college and health and safety. This study examined differences in general stress, cognitive appraisals of the pandemic (e.g., viewing the pandemic as threatening or uncontrollable), and pandemic-specific stress between southeastern college students with and without disabilities. Analyses of covariance revealed group differences in general stress, threat appraisal of the pandemic, and pandemic-specific stress related to academics, larger societal concerns (e.g., economy, death toll), concern for loved ones' well-being, financial issues, health and safety concerns, mental health concerns, uncertainty about the future, concern regarding access to medical resources, and technology concerns. Participants with disabilities viewed the pandemic as more threatening and stressful than those without a disability. Participants with comorbid mental health, learning, and/or physical disabilities reported greater threat and stress compared to other groups, with those with a mental health disability only also showing this pattern. As policies related to course formats and COVID-19 safety precautions change, further examination of pandemic appraisals and stress should continue in order to provide recommendations to student support professionals.