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Doxycycline is a widely used antibiotic for commonly encountered infections and is generally well tolerated. However, it is associated with rare, drug-induced severe thrombocytopenia, which, if not promptly recognised and managed, could prove fatal. We present a case of doxycycline-induced severe thrombocytopenia in a 63-year-old man with a background of type 2 diabetes mellitus, left ventricular systolic dysfunction, and hypothyroidism. The platelet count dropped to a critical level of 6 x 10⁹/L following a one-week course of doxycycline, which improved with drug withdrawal, platelet transfusions, and a course of high-dose steroid therapy over three weeks. This was evidenced by a Naranjo Adverse Drug Reaction Probability Scale score of 8/13, which is the upper limit for a probable adverse drug reaction. This rare but life-threatening side effect of doxycycline highlights the need for a follow-up blood test shortly after commencing therapy for early detection and prompt management.