The estimation of the early post-mortem interval (PMI) in human corpses remains a challenging goal for forensic sciences. By exploiting label-free Raman mapping on non-treated human whole blood directly deposited on innovative nanostructured Surface Enhanced Raman Scattering (SERS) substrates, we propose a novel approach to rapidly obtain information on the presence of different levels of hypoxanthine (Hx) as a post-mortem biochemical marker (BPM). The efficacy of the method was tested on several whole blood samples from human corpses, spanning a time window between 3 and 32 h after death. The methodology, which allows the identification of metabolic and endogenous sources of Hx concentration increase, can be further engineered to develop dedicated automatable devices and holds potential for on-field applications during medical and forensic site inspections and investigations.