This qualitative study assessed the knowledge and beliefs surrounding fever syndrome among adult febrile patients seeking health care in Kilombero, Tanzania. From June 11 to July 13, 2014, 10% of all adult (≥ 15 years) febrile patients enrolled in the larger syndromic study, who presented with an axillary temperature ≥ 37.5°C and symptom onset ≤ 5 days prior, were randomly selected to participate in an in-depth physician-patient interview, informed by Health Belief Model constructs. Interviews were audio recorded, translated, and transcribed. Transcripts were coded using NVivo Version 11.1, and the thematic content was analyzed by two separate researchers. Blood and nasopharyngeal/oralpharyngeal specimens were collected and analyzed using both acute febrile illness and respiratory TaqMan Array Cards for multipathogen detection of 56 potential causative agents. A total of 18 participants provided 188 discrete comments. When asked to speculate the causative agent of febrile illness, 33.3% cited malaria and the other 66.6% offered nonbiomedical responses, such as "mosquitoes" and "weather." Major themes emerging related to severity and susceptibility to health hazards included lack of bed net use, misconceptions about bed nets, and mosquito infestation. Certain barriers to treatment were cited, including dependence on traditional healers, high cost of drugs, and poor dispensary services. Overall, we demonstrate low concurrence in speculations of fever etiology according to patients, clinicians, and laboratory testing. Our findings contribute to the important, yet limited, base of knowledge surrounding patient risk perceptions of febrile illness and underscore the potential utility of community-based participatory research to inform disease control programs.