Malaria is the leading cause of death and economic burden worldwide. Current diagnostic methods rely on microscopy and blood-based rapid diagnostic tests. A common rapid diagnostic test target is Plasmodium falciparum histidine-rich protein 2 (PfHRP2), a parasite protein released into the host's blood during Plasmodium infection; it has also been detected in saliva, although results have been inconsistent. This pilot study quantified plasma and salivary PfHRP2 antigen levels and assessed their associations with age, parasite density, and clinical malaria status in a malaria-endemic region of western Kenya with high transmission. This pilot study enrolled 34 patients with acute uncomplicated malaria. Paired blood and saliva samples were collected at enrolment, with repeat sampling 4 weeks after treatment. P. falciparum infection was confirmed by light microscopy, and PfHRP2 concentrations were measured using an enzyme-linked immunosorbent assay. Data were analyzed in R version 4.5.2. Spearman’s rank correlation and robust linear regression were used to examine the relationship between plasma and salivary P. falciparum antigen levels in individuals with acute malaria and to assess whether PfHRP2 concentrations in either matrix predicted parasite density, clinical malaria status, and age. Salivary PfHRP2 levels did not significantly predict parasite density or age (χ²=0.54, P=0.76). By contrast, plasma PfHRP2 levels strongly predicted both parasite density and age (P=0.034). Plasma and salivary PfHRP2 concentrations were not significantly correlated (ρ=-0.327, P=0.059). Nevertheless, routine measurement of salivary PfHRP2 using more sensitive methods may improve diagnosis and guide treatment management.