Mental health and wellness research continue to be a topic of importance among veterinary students in the United States of America (US). Limited peer reviewed literature focusing on South African veterinary students is available. South African veterinary medical students might benefit from approaches to improve mental health and wellness similar to those recommended in the US. However, these recommendations may not address the underlying risk factors for mental health and wellness concerns or mismatch resources available to South African veterinary medical students. The purpose of this collaborative study was to compare the mental health and wellness among veterinary students enrolled at the University of California, Davis (UCD), and the University of Pretoria (UP), the only veterinary school in South Africa. Our primary research question was; Are the measures of mental health and wellness for students at similar stages in the veterinary curriculum different between the two schools? We hypothesized that mental health and wellness as determined by assessment of anxiety, burnout, depression, and quality of life between the two schools is different. A cross-sectional study of 102 students from UCD and 74 students from UP, at similar preclinical stages (Year 2 for UCD and Year 4 for UP) of the veterinary curriculum was performed. Anxiety, burnout, depression, and quality of life were assessed using the Generalized Anxiety Disorder (GAD-7), Maslach Burnout Inventory (MBI), Patient Health Questionnaire (PHQ-9), and Short Form-8 (SF-8), respectively. Students from both schools had moderate levels of anxiety, high levels of burnout, mild to moderate levels of depression, poor mental health, and good physical health. Our results suggest that similar mental health and wellness concerns in South African veterinary students is comparable with concerns in veterinary medical students in the US. Recommendations and resources to improve mental health and wellness in US veterinary medical students might be applicable to South African veterinary medical students.