The population of Immokalee in Southwest Florida is 75% Latinos, with nearly half being foreign-born. Several documented stressors contribute to poor mental health among Latinos. However, little is known about Latinos’ mental health in this region. This study sought to assess self-rated mental health (SRMH) and acculturation stress (AS) and predict SRMH based on stress from life events, AS, sociodemographic characteristics, and social support among U.S.-born and foreign-born Latinos. Face-to-face interviews and assisted self-administered surveys were used to collect information among 158 Latinos on sociodemographic characteristics, AS, major life events that caused stress, social support, and SRMH. AS was elicited by asking three questions (Cronbach’s a = .84), total stress level was determined by 10 major life events, and social support was elicited by 14 questions (Cronbach’s a = .76). Results indicated that foreign-born Latinos 36–75 years old, with minimal social support, U.S.-born Latinos with lower educational levels, minimal social support, and high-moderate stress levels reported statistically significant low SRMH. AS was significantly higher among foreign-born 36- to 75-year-olds, with lower educational levels, minimal social support, who preferred the Spanish language and lived ≤15 years in the United States. Linear regression analysis showed social support, educational levels, and life stressors to be significant predictors of SRMH among U.S.-born Latinos, whereas social support was a significant predictor in foreign-born Latinos.