The clinical empiricism of Thomas Sydenham (1624–1689) and his definition of especie morbosae represented a substantial turn in the medicine of his time. This turn supposed the shift towards an ontological conception of diseases, from a qualitative to quantitative interpretation. Sydenham’s clinical proposal had a great influence on empiricism philosophical thinking, particularly in John Locke and his delimitation of knowledge. The dialogue between medicine and philosophy, set out by Sydenham-Locke, reactivates the problem of the clinical and theoretical foundations of medical thought, as well as the limits of scientific knowledge. Similar to problem exposed in the Hippocratic treatise On ancient medicine, seventeenth-century medicine seeks its epistemological foundations and the solution to its difficulties in clinical experience, probability and analogy. The aim of this work is to show the Sydenham’s contribution to one of the great controversies between medicine and philosophy.