An unstable bilirubin level in the human blood causes many dangerous health problems, such as jaundice, coronary artery disease, ulcerative colitis, and brain lesions. Therefore, the accurate and early detection of bilirubin concentrations in the blood is mandatory. In this work, a highly sensitive biosensor based on photonic crystal fiber (PCF) for monitoring bilirubin levels is proposed and analyzed. The sensor parameters, including relative sensitivity, effective mode area, confinement loss, and effective material loss, are calculated. The geometrical parameters are studied, and a modal analysis of the suggested sensor is carried out using the full-vectorial finite element method (FEM). The fabrication tolerance of the geometrical parameters is also studied to ensure the fabrication feasibility of the reported design. High sensitivities of 95% and 98% are obtained for the x-polarized and y-polarized modes, respectively. Furthermore, a small material loss of 0.00193 cm−1, a small confinement loss of 2.03 × 10−14 dB/cm, and a large effective mode area of 0.046 mm2 are achieved for the y-polarized mode. It is believed that the presented sensor will be helpful in health care and in the early detection of bilirubin levels in the blood.