Purpose: There have been recent advances to the adoption of pre-exposure prophylaxis (PrEP) as an effective human immunodeficiency virus (HIV) preventive treatment among men who have sex with men, but PrEP services and resources are often not accessible to those who are deaf and use American Sign Language (ASL). This article investigates PrEP knowledge among deaf gay, bisexual, and queer (GBQ) men and the contribution of social support to their perceptions regarding the effectiveness of PrEP at preventing HIV. Methods: An online health survey in ASL and English included questions about sexual orientation, HIV testing, PrEP knowledge and perceived effectiveness at preventing HIV, coming out to healthcare providers, and social support. We gathered data from 121 deaf GBQ men recruited from diverse cities in the United States, with 87% self-identifying as gay. Logistic regression analyses were used to examine the relationships between self-reported level of social support and perceived effectiveness of PrEP at preventing HIV after controlling for sociodemographic and health-related variables. Results: There was a significant relationship between meeting new lesbian, gay, bisexual, transgender, and queer (LGBTQ) friends online and PrEP knowledge (v 2 = 14.93; p < 0.001). After controlling for sociodemographic and health-related variables, those who discussed LGBT-related issues online and/or on a social networking site regularly were threefold more likely to perceive PrEP as being effective at preventing HIV than those who did not engage in online discussions (odds ratio = 3.12; 95% confidence interval: 1.12-8.75). Conclusion: For deaf GBQ men, PrEP knowledge might be attained through meeting and making new LGBTQ friends online. Active engagement in online discussions about LGBT-related issues might enhance perceptions regarding the effectiveness of PrEP to prevent HIV.