The clinical manifestations of dengue fever (DF) and malaria are similar. Specific diagnostic tests are not always available. A retrospective study to compare the laboratory results of malaria and DF was conducted at the National Center for Global Health and Medicine in Japan from January of 2005 to March of 2013. Febrile returned travelers from overseas diagnosed with malaria or DF were included; 86 malaria and 85 DF cases were identified. C-reactive protein (CRP) and total bilirubin (T-bil) had high area under the receiver operating characteristic curves (> 0.9). A cutoff value of CRP > 2.4 mg/dL to predict malaria as opposed to DF had a sensitivity of 91.9% (95% confidence interval [95% CI] = 83.9-96.7%) and specificity of 90.6% (95% CI = 82.3-95.8%). A cutoff value of T-bil > 0.9 mg/dL to predict malaria as opposed to DF had a sensitivity of 73.8% (95% CI = 62.7-83%) and a specificity of 95.1% (95% CI = 88-98.6%). CRP and T-bil are useful to distinguish between DF and malaria in returned travelers.