The primary objective of this study is to determine the effect of silicon wafer processing parameters on giant magnetoresistance (GMR). Thermally oxidized silicon wafers serve as substrates for alternating layers of NiFeCo and Cu (2.0–2.5 nm). SiO2films prepared in the laboratory are loaded into the sputtering chamber along with commercially oxidized wafers for comparison purposes. Four process parameters are systematically varied—oxidation method, postoxidation anneal (POA), oxide thickness, and oxidation temperature. Preliminary results indicate the two most influential processing parameters are the method of oxidation (dry oxygen or wet steam) and a POA. In contrast, GMR values do not seem to vary greatly for various oxidation or POA temperatures in the range 800–1000 °C. We present GMR results of NiFeCo/Cu multilayers on oxidized silicon substrates formed by various processing methods. GMR is observed for all films, with the magnitude of the effect increasing for substrates oxidized by ‘‘wet’’ methods and oxidized substrates that include a POA (1000 °C, nitrogen atmosphere, 20 min) previous to sputter deposition of the multilayers. Our data suggest that the GMR of the multilayer stack is sensitive to changes at the Si–SiO2interface.