To explore sexual health knowledge among Latino immigrants in a Southern U.S. city, we conducted 20 qualitative interviews, (10 Women and 10 Men). We explored knowledge and factors associated with sexual health among male and female Latino immigrants in a Southern U.S. city experiencing a major growth of Latino immigrants in the past 10 years. Both genders demonstrated limited knowledge of Human Papillomavirus (HPV) and risks of sexually transmitted infection (STI) acquisition. Neither gender perceived that they could have an asymptomatic STI, including HPV. Gender differences exist in sexual behaviors and perceptions of STI risk. Females indicated that female Latinas tend to have older sexual initiation age, fewer lifetime sexual partners and more pro-active sexual health than did Latinos when referring to Latino males. Consequently, male and female Latino immigrants could benefit from culturally relevant programs to alleviate STI disparities. © Springer Science+Business Media, LLC 2012.