We present a fiber-optic sensor based on the principles of a Fabry–Perot interferometer (FPI), which promptly, sensitively, and precisely detects blood clot formation. This sensor has two types of sensor tips; the first was crafted by splicing a tapered fiber into a single-mode fiber (SMF), where fine-tuning was achieved by adjusting the tapered diameter and length. The second type is an ultra-compact blood FPI situated on the core of a single-mode fiber. The sensor performance was evaluated via clot-formation-indicating spectrum shifts induced by the varied quantities of a thrombin reagent introduced into the blood. The most remarkable spectral sensitivity of the micro-tip fiber type was approximately 7 nm/μL, with a power sensitivity of 4.1 dB/μL, obtained with a taper fiber diameter and length of 55 and 300 μm, respectively. For the SMF type, spectral sensitivity was observed to be 8.7 nm/μL, with an optical power sensitivity of 0.4 dB/μL. This pioneering fiber-optic thrombosis sensor has the potential for in situ applications, healthcare, medical monitoring, harsh environments, and chemical and biological sensing. The study underscores the scope of optical technology in thrombus detection, establishing a platform for future medical research and application.