In this paper, a D-shaped photonic crystal fiber (PCF) sensor based on surface plasmon resonance with a micro-rectangular opening is proposed. The micro-rectangular opening introduces strong coupling between the metal layer and the core-guided mode as it helps in reducing the distance between the sensing channel and the core of the PCF. Gold (Au) is a noble plasmonic material, which is deposited on the micro-rectangular opening in order to generate an ample amount of surface plasmon on the micro-opening area’s surface. This micro opening also allows for the ease of fabrication while maintaining strong bio-detection capabilities. The obtained results as maximum wavelength sensitivity, resolution, and figure of merit are 67,000 nm/RIU, <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${1.5} \times {10}^{-{6}}$ </tex-math></inline-formula> RIU and 279.16 RIU <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$^{-{1}}$ </tex-math></inline-formula> respectively. These results indicate that they are significantly finer than those existing in the related state of the art, and that the proposed fiber sensor is easy to fabricate. Further, the proposed fiber sensor is utilized for the detection of malaria disease. The proposed sensor’s computed sensitivities for ring stage, trophozoite stage, and schizont stage RBCs of malaria disease are 25,715.30 nm/RIU, 33,157.89 nm/RIU, and 44,827.58 nm/RIU, respectively.