Nigerians are an integral part of the nursing profession, yet there is no literature on their common health risks, such as homesickness, isolation and suicide ideation. The purpose of this study was to investigate the association between lack of acculturation, social support, and self-esteem and mental health among Nigerian nursing students. Berry’s model of acculturation was used which identifies individuals perception of self in relation to their ethnic culture and the host culture. A sample of 76 Nigerian nursing students enrolled in Baccalaureate nursing programs from 3 universities in the District of Columbia and Maryland participated in the study. Data were obtained using an online survey of 69 items assessing their acculturation, social support, self-esteem and their mental health. A descriptive cross sectional design was used. Analysis of the data included descriptive statistics, Pearson correlation, multiple regression, and ANOVA. The final regression model revealed that acculturation, companionship construct of social support and self-esteem are predictors of mental health status as shown by the adjusted R squared (R² = 0.638). Recommendations are for universities to commit to increasing acculturation, social support, and self-esteem among foreign students in an effort to decrease isolation and improve their mental health. It is also recommended that future studies should be conducted on social isolation of subcultures to improve acculturation and reduce incidence of low self-esteem among foreign students within the American society. The strategies would create positive social change for healthcare organizations and nurse educators, resulting in an increase of ethnic diverse nurses and reducing the shortage of nurses in the USA.