Malaria, arbovirus infection and travelers' diarrhea are among the most common etiologies of fever after a stay in the tropics. Because the initial symptoms of these diseases often overlap, the differential diagnostic remains a challenge. The aim of this study was to establish the effectiveness of platelet and leukocyte counts in the differential diagnosis of fever in the returning traveler. Between 2013 and 2016, patients with a clinical suspicion of malaria, who had thick blood smears performed were retrospectively included. The microbiological etiology of each episode was established based on molecular detection in the case of arbovirus infection, the detection of pathogens in stool samples for diarrhea and other gastrointestinal symptoms and the thick and thin blood smear results for malaria. A total of 1,218 episodes were included. Malaria, arbovirus infection, and diarrhea and other gastrointestinal symptoms caused 102 (8.4%), 68 (5.6%), and 72 (5.9%) episodes, respectively. The median platelet counts in malaria episodes were 89 × 109/L and thrombocytopenia (< 150,000 × 109 platelets/L) yielded a 98% negative predictive value to predict malaria. The median leukocyte counts in arbovirus infection episodes were 3.19 × 109/L and leucopenia (< 4 × 109 leukocytes/L) yielded a 97.9% negative predictive value to predict arbovirus infections. Platelet and leukocyte counts were not significantly altered in episodes caused by diarrhea and other gastrointestinal symptoms. Initial platelet and leukocyte counts might be useful for the clinical differential diagnosis of fever in the returning traveler. Although these results are insufficient to establish a diagnosis, they should be considered in the initial clinical assessment.