We perform numerical simulations of single-phase and two-phase models of a direct methanol microfluidic fuel cell (μ-DMFC). The focus of this study is on the parametric analysis of a single channel of the system, for specific sets of operating conditions, in order to map the dependence of the cell performance with respect to the geometrical parameters. Different geometries, ranging from 500 μm to 4 mm in width, and 500 μm to 4 cm in length, along with membrane thicknesses from 50 μm to 500 μm, were considered. The mathematical models are given in terms of the Navier-Stokes, the Butler-Volmer and the Maxwell-Stefan equations, along with Darcy’s equation for the flow across the membrane. The difference between the single- and two-phase flow models lies upon the specific constitutive equations used. For each geometry and operating condition, the two-dimensional equations were solved by a finite element method. The conditions of operation include: flow rates and inlet weight fractions of methanol at the anode and oxygen the cathode. The results from this analysis, presented as polarization curves and power densities, indicate that fuel-cell systems with higher flow rates and inlet weight fraction of methanol achieve the best performance. However, when the concentration of methanol exceeds 2M the cell performance is negatively impacted due to crossover. Comparison of the results indicates that the two-phase model has a more restrictive domain for both the geometrical parameters and operating conditions.