The growing homeless population in the U.S.A. is disproportionately impacted by poor mental and physical health status, including a higher incidence of acute and chronic health problems, increased hospitalizations, and premature mortality compared to the general population. This study examined the association between demographic, social, and clinical factors and perceptions of general health status among the homeless population during admission to an integrated behavioral health treatment program. The study sample included 331 adults experiencing homelessness with a serious mental illness or co-occurring disorder. Participants were enrolled in services at a day program for unsheltered homeless adults, a residential substance use treatment program for males experiencing homelessness, a psychiatric step-down respite program for those experiencing homelessness following psychiatric hospitalization, permanent supportive housing for formerly chronically homeless adults, a faith-based food distribution program, and homeless encampment sites in a large urban area. Participants were interviewed using The Substance Abuse and Mental Health Services Administration's National Outcome Measures tool and a validated health-related quality of life measurement tool, SF-36. Data were examined using in elastic net regression. The study found seven factors to be particularly strong predictors of SF-36 general health scores.Male gender, "other" sexual identity, stimulant use, and Asian race were all associated with better perceptions of health status, while transgender status, inhalant use, and number of times arrested were associated with poorer perceptions. This study suggests targeted areas for health screening within the homeless population; however, more studies are necessary to demonstrate generalizability of the results.