Fever is typically treated empirically in rural Mozambique. We examined the distribution and antimicrobial susceptibility patterns of bacterial pathogens isolated from blood-culture specimens, and clinical characteristics of ambulatory HIV-infected febrile patients with and without bacteremia. This analysis was nested within a larger prospective observational study to evaluate the performance of new Mozambican guidelines for fever and anemia in HIV-infected adults (clinical trial registration NCT01681914, www.clinicaltrials.gov); the guidelines were designed to be used by non-physician clinicians who attended ambulatory HIV-infected patients in very resource-constrained peripheral health units. In 2012 (April-September), we recruited 258 HIV-infected adults with documented fever or history of recent fever in three sites within Zambézia Province, Mozambique. Although febrile patients were routinely tested for malaria, blood culture capacity was unavailable in Zambézia prior to study initiation. We confirmed bacteremia in 39 (15.1%) of 258 patients. The predominant organisms were non-typhoid Salmonella, nearly all resistant to multiple first-line antibiotics (ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole). Features most associated with bacteremia included higher temperature, lower CD4+ T-lymphocyte count, lower hemoglobin, and headache. Introduction of blood cultures allowed us to: 1) confirm bacteremia in a substantial proportion of patients; 2) tailor specific antimicrobial therapy for confirmed bacteremia based on known susceptibilities; 3) make informed choices of presumptive antibiotics for patients with suspected bacteremia; and 4) construct a preliminary clinical profile to help clinicians determine who would most likely benefit from presumptive bacteremia treatment. Our findings demonstrate that in resource-limited settings, there is urgent need to expand local microbiologic capacity to better identify and treat cases of bacteremia in HIV-infected and other patients, and to support surveillance. Data on the prevalence and susceptibility patterns of important pathogens can guide national formulary and prescribing practices.