Three-dimensional hydrodynamic losses are assessed in this investigation for a foil oscillating sinusoidally in a combined heave and pitch motion with large amplitudes. Simulations are performed using a unsteady Reynolds-Averaged-Navier-Stokes (URANS) solver on an oscillating foil in a power-extraction mode; thus acting as a hydrokinetic turbine at high Reynolds number. Foils of various aspect ratios (span to chord length ratio) are considered, both with and without endplates for one representative operation point. Hydrodynamic forces and extracted power are compared with results from the equivalent two-dimensional (2D) computations. It is found that the relative drop of performance (cycle-averaged power extracted) due to 3D hydrodynamic losses can be limited to 10% of the 2D prediction when endplates are used on a foil of aspect ratio greater than ten. The practical consideration of an oscillating-foil hydrokinetic turbine operating in an imperfectly-aligned upstream water flow is also addressed with simulations considering an upstream flow at a yaw angle up to 30° with respect to the foil chord line. Effects on performance are found to be proportional to the projected kinetic energy flux.