This study examined the impact of acculturation stress and work-family conflict on the mental health of Ghanaian immigrants in the United States (US). One hundred participants were recruited from two US states to investigate the relationship between acculturation stress, work-family conflict, and mental health among this population. Drawing from the concepts of sociocultural theory, I proposed three hypotheses: (1) High acculturation stress will lead to high work-family conflict, (2) High work-family conflict will result in poor mental health and (3) Work-family conflict will mediate the relationship between acculturation stress and mental health. The results fully supported the first hypothesis and partially supported the second and third. High acculturation stress led to high work-family conflict. Although high work-family conflict resulted in poor mental health, strong family or other support mediated workfamily conflict and mental health. Participants who reported poor mental health also reported lacking family or other support and those who reported strong family support also reported good mental health even with high work-family conflict. The latter group expected their mental health to remain good or improve overtime. I draw on these findings to conclude that Ghanaian immigrants in the US experience significant acculturation stress and work-family conflict leading to poor mental health if they lack good family. These findings have implications for healthcare practitioners who see members of this population.