An accurate SO(2) prediction method for using broadband continuous-wave diffuse reflectance near infrared (NIR) spectroscopy is proposed. The method fitted the NIR spectra to a Taylor expansion attenuation model, and used the simulated annealing method to initialize the nonlinear least squares fit. This paper investigated the effect of potential spectral interferences that are likely to be encountered in clinical use, on SO(2) prediction accuracy. The factors include the concentration of hemoglobin in blood, the volume of blood and volume of water in the tissue under the sensor, reduced scattering coefficient, µ(s)', of the muscle, fat thickness and the source-detector spacing. The SO(2) prediction method was evaluated on simulated muscle spectra as well as on dual-dye phantoms which simulate the absorbance of oxygenated and deoxygenated hemoglobin.