To examine the cultural limitations and implications in the applicability of the Depression Anxiety Stress Scale 8-items (DASS-8)-a shortened version of the DASS-21 recently introduced in an Arab sample-this study evaluated its psychometric properties, including measurement invariance, among healthy subjects from the United States, Australia, and Ghana. Confirmatory factor analysis revealed good fit of the DASS-8 relative to a 12-item version (DASS-12). Both the DASS-8 and the DASS-12 were invariant at all levels across genders, employment status, and students vs. non-students. The DASS-8/DASS-12 also expressed invariance at the configural and metric levels across all countries, albeit scalar invariance was not maintained due to misspecification of the factor loadings in the Ghanian sample. Mann-Whitney U test revealed significantly lower levels of mental symptomatology on the DASS measures among Ghanian students than in English-speaking respondents (both students and non-students). The DASS-8 expressed excellent internal consistency (coefficient alpha = 0.89), good convergent validity-noted by high values of item-total correlations ( = 0.87 to 0.88), good predictive validity-indicated by significantly strong correlation with the DASS-21 and its subscales ( = 0.95 to 0.80), and adequate discriminant validity-indicated by heterotrait-monotrait ratio of correlations <0.85. The DASS-8 correlated with the Internet Gaming Disorder-9, the Adult attention-deficit/hyperactivity disorder Self-Report Scale, and the Individualism and Collectivism Scale/Culture Orientation Scale at the same level as the DASS-21 and the DASS-12, denoting its adequate criterion validity. The DASS-8 can be used as a brief alternative to the DASS-21 to screen for mental symptomatology in English-speaking and African cultures. However, the same scores on the DASS-8 and the DASS-12 may not always indicate the same level of symptom severity in subjects from different countries. Further inter-cultural evaluations of the DASS-8 are needed.