BACKGROUND People with serious mental illness have rates of Human Immuno-deficiency Virus (HIV) infection higher than expected in the general population for the same demographic area. Despite this elevated prevalence, UK national strategies around sexual health and HIV prevention do not state that people with serious mental illness are a high risk group. However, a significant proportion in this group are sexually active and engage in HIV-risk behaviours including having multiple sexual partners, infrequent use of condoms and trading sex for money or drugs. Therefore we propose the provision of HIV prevention advice could enhance the physical and social well being of this population. OBJECTIVE To assess the effects of HIV prevention advice in reducing morbidity, mortality and preserving the quality of life in people with serious mental illness. METHODS We searched the Cochrane Schizophrenia Group's Trials Register (24 January, 2012), which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There is no language, date, document type, or publication status limitations for inclusion of records in the register. METHODS We planned to include all randomised controlled trials focusing on HIV prevention advice versus standard care or comparing HIV prevention advice with other more focused methods of delivering care or information for people with serious mental illness. METHODS Review authors (NW, AC, AA, GT) independently screened search results and did not identify any studies that fulfilled the review's criteria. RESULTS We did not identify any randomised studies that evaluated advice regarding HIV for people with serious mental illness. The excluded studies illustrate that randomisation of packages of care relevant to both people with serious mental illness and HIV risk are possible. CONCLUSIONS Policy makers, clinicians, researchers and service users need to collaborate to produce guidance on how best to provide advice for people with serious mental illness in preventing the spread of HIV infection. It is entirely feasible that this could be within the context of a well-designed simple large randomised study.