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Infective endocarditis (IE) remains a severe condition with high morbidity and mortality, often complicated by metastatic infections. Spinal involvement, particularly spondylodiscitis (SD) and epidural or paraspinal abscesses, is increasingly recognized but frequently underdiagnosed. We report two cases of mitral valve IE complicated by SD. A 77-year-old woman with culture-negative IE underwent urgent mitral valve replacement; subsequent magnetic resonance imaging revealed L3-L4 SD and a large right psoas abscess managed conservatively with prolonged antibiotics. A 73-year-old woman presented with cardioembolic stroke and severe mitral regurgitation; spinal MRI showed L4-L5 SD and a long-segment epidural abscess requiring urgent neurosurgical decompression, followed by valve replacement. Both cases highlight diagnostic challenges in culture-negative IE and underscore the need for early multimodality imaging, guideline-directed antimicrobial therapy, and multidisciplinary management. Timely recognition and intervention are essential to prevent irreversible neurological deficits and optimize outcomes.