Every year, more than one million individuals die from malaria, an infection spread by mosquitoes infected by haemoparasites with only one cell of the Plasmodium class. In this work, a photonic crystal fibre (PCF)-based refractive index (RI) biosensor for the early detection of malaria in individuals, using red blood cell (RBC) variation monitoring, is presented. The proposed PCF includes three layers of hexagonal lattices of elliptical air holes and also contains a small vertical elliptical channel in which the RBC samples are placed. Because of the RI difference between samples from both healthy and malaria-infected human RBCs, the peak wavelength of infected RBC samples differs from that of normal RBC samples. From calculation, the achieved wavelength sensitivities of the biosensor are 3571.42 nm/RIU, 3157.89 nm/RIU, and 3103.44 nm/RIU in the x-polarized direction and 2857.14 nm/RIU, 2631.57 nm/RIU, and 2758.6 nm/RIU in the y-polarized direction in different phases—ring, trophozoite, and schizont respectively—with a highest possible detection limit of 0.029. Because of the small detection limit and high sensitivity, the proposed PCF biosensor has enhanced sensing abilities that make it suitable for primary diagnosis of malaria. With its high sensitivity and low detection limit, this PCF biosensor has improved sensing capabilities that make it appropriate for malaria diagnosis at the outset.