Thermally oxidized porous silicon particles have been widely studied as drug delivery systems for sustained release. In this work, TOPSip with different particle and pore dimensions were synthesized by electrochemical etching and used as microcarriers to sustain tramadol hydrochloride, a centrally acting opiate analgesic. The physicochemical and morphological properties of nanostructured TOPSip were fully characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectrometry and zeta potential. Modulation of the etching parameters allowed the control of the nano-pore size from 6 nm to 33 nm and particle size from 0.8 to 31 μm. Furthermore, TR loading capacity in TOPSip-OH was quantified by UV–Vis spectroscopy. TOPSip-OH with the smallest pore size exhibited a TR loading capacity of 10%. In contrast, TOPSip-OH with the highest pore dimensions showed an increase in the loading capacity of tramadol up to 31%. TR release was carefully studied in simulated gastric (pH 1.2) and intestinal fluids (pH 6.8). The released profiles demonstrated that microparticles with ∼6 nm pore size exhibited a sustained release up to 24 h with burst effect depending on pH. Release profiles of composites were compared with those obtained from a commercial extended-release tramadol formulation in both pH. It was observed that commercial composite released TR entirely after 1 h. TR cumulative release data were fitted using different mathematical models. Korsmeyer-Peppas fitted well for both simulated fluids. Through in vivo assessment, it was demonstrated that TR-loaded TOPSip sustains antinociceptive and anti-inflammatory effects compared to administration of tramadol at the same dose, which is a novel contribution of this work.