In this paper, surface plasmon resonance curves of an optical fiber-based sensor were investigated. From an experimental and theoretical perspective, the response curves were analyzed and discussed. Precisely, such curves were calculated by modeling the analyte/metallic layer interface using a multilayer system, including the effects of roughness. Then, the experimental response curves observed in solutions with different refractive indices were compared to the simulated curves. Good agreement was obtained with respect to the resonance peak location and the shape of the curves. Consequently, these results enabled us to predict the ideal functioning conditions of the sensor, i.e., the working parameters corresponding to the best sensitivities of detection.