Background: In the last 6 months, cases of acute hemorrhagic fever (AHF) have been recorded in Sao Tome and Principe (STP). Objective: To identify the clinical, epidemiological and laboratory parameters associated with AHF cases found in patients hospitalized in STP. Methods: Descriptive and quantitative analysis of AHF cases hospitalized in STP in the period December 2021 to May 19, 2022 through the variables: demographic data; clinical data; laboratory data and clinical outcome. Results: Analyzed 18 of 22 AHF cases, 50% of them male, mean age 33.7 years, 85.7% residing in the 2 largest districts of the country, 66.7% rural workers, administrative near maritime areas, sailors and domestics. 66.7% were healthy individuals. ≥50% had a fever, asthenia/weakness, myalgia, headache, lethargy, nausea, vomiting, and diarrhea. 22.2% to 33.3% had retro-orbital pain, abdominal pain, decreased consciousness, dyspnea/hypoxia, and cough. In a smaller register (5.6% - 11.1%), exanthema, convulsion, arthralgia, low back pain, chills, and chest pain. Bleeding from the digestive tract was found in 72.2%, followed by vaginal (33.3%), urethral (27.8%), nasal (22.2%), and oral (16.7%). 50% had laboratory confirmation for dengue, and another 50% with suspected clinical diagnosis without laboratory confirmation of the etiologic agent. Despite hemorrhage, 66.7% of confirmed cases were hemodynamically non-severe, and 88.9% of suspected cases were severe. Coinfection with malaria is evidenced in 11.1% of cases. 72.2% recovered and 27.8% died (deaths in 55.5% of suspected cases). Case deaths were male (100%), resident foreigners (40%), tool store employees, sailors and students, healthy (80%), and residing in the largest district in the country (60%). All deaths were hospitalized in serious condition, 80% were hospitalized for hemorrhage and shock, with bleeding arising between day 4 - 5 of illness in 60% and hospitalization on day 5 of illness. 60% died within ≤24 hours of hospitalization. 80% died from shock and multi-organ dysfunction and 20% from respiratory failure. Deaths had thrombocytopenia (100%), renal dysfunction (100%) and significantly increased transaminases (100%), anemia (75%) and leukocytosis (66.7%). 20% had a radiological change of pulmonary infiltrates. Conclusion: Our data reveal the complexity of the pathogens causing AHF and suggest the possible presence of other human pathogens usually unknown in the Santomean geographical territory.