Abstract Background As a widely accepted field standard diagnostic tool for malaria, microscopic examination is often difficult to perform in resource-poor settings. The immunochromatographic HRP2/pLDH (Pf/Pan) Rapid Diagnostic Tests (RDTs) serve as alternatives to microscopic examination for falciparum and non-falciparum malaria in co-endemic areas by detecting the histidine-rich protein 2 (HRP2) and pan-plasmodial lactate dehydrogenase (pLDH) antigen. However, Pf/Pan RDTs do not directly quantify parasitaemia. In this study, the diagnostic performance of Pf/Pan RDT and its association with parasite density was examined. Methods Blood smears from patients who were screened for PRIMA Clinical Trial (Trial Registration Number: NCT03916003) conducted in East Sumba, Indonesia, and enrolled to its sub-study, ACROSS, were examined for microscopic examination and RDT using CareStart™ Malaria HRP2/pLDH (Pf/PAN) Combo (CareStart™ Pf/Pan RDT). Results were analysed for both diagnostic performance of RDT and its relationship with parasite density using a logistic regression model. Results 317 participants were included in this study and 158 (49.8%) were malaria positive by microscopy. Among all malaria-positive participants, Plasmodium falciparum infections accounted for 149 (94.3%) cases. The sensitivity and specificity of HRP2 band were 97.3% (95% CI 93.3–99.2) and 97.6% (95% CI 94.0–99.4), respectively, while that of pLDH band were 87.3% (95% CI 81.1–92.0) and 100% (95% CI 97.7–100). For each ten-fold increase in parasite density, the RDT had 12 times the odds of returning Pf/Pan-positive results (n = 126) compared to Pf-positive (n = 19) (OR: 12.1; 95% CI 5.18 to 34.8; p < 0.001). Conclusions CareStart™ Pf/Pan RDT is reliable in diagnosing falciparum malaria and Pf/Pan-positive results indicate higher parasite density. Pf/Pan-positive results should alert the clinical staff of the increased risk of poor clinical outcome, and should be prioritized for microscopic examination compared to Pf-positive results.