This paper presents a novel rectangular hybrid plasmonic waveguide sensor for the detection of malaria-infected red blood cell (RBC) stages in human blood based on the localized surface plasmon resonance (LSPR) phenomenon. The proposed structure consists of a silicon substrate integrated with a SiO2 dielectric layer and a gold nanorod, where the analyte region acts as the sensing medium. The sensor performance is systematically evaluated for different malaria infection stages, namely ring, trophozoite, and schizont, in comparison with healthy RBCs over the wavelength range of 600–1000 nm. The design exhibits significant resonance wavelength shifts and confinement loss variations for different infection stages, enabling effective and reliable differentiation. A maximum wavelength sensitivity of 517 nm/RIU is achieved for the schizont stage, while sensitivities of 263 nm/RIU and 142 nm/RIU are obtained for trophozoite and ring stages, respectively. Furthermore, the sensor response is analyzed using air and deionized (DI) water as reference analytes, demonstrating substantial amplitude sensitivity enhancements. These results highlight the strong light–matter interaction in the proposed structure and confirm its potential for highly sensitive, compact, and early-stage malaria detection in biomedical and point-of-care diagnostic applications.