We assess the ability of predicted seismic velocities (Vp, compressional wave; Vs, shear wave; and Vp/Vs) to identify regions in the upper mantle that are enriched in orthopyroxene relative to normal melt-depleted peridotite compositions. Orthopyroxene enrichment has been found in mantle xenoliths from a number of locations, including the Colorado Plateau and the Kaapvaal craton. We find that the Vp/Vs ratio is very sensitive to orthopyroxene concentration, but it is not sensitive to depletion level. We compare these predicted velocities and Vp/Vs ratios to the high Vs, low Vp/Vs anomaly found above the central Chile–Argentina flat slab. Within error, the predicted velocities of some of the orthopyroxene-enriched xenoliths match the observed velocities from the Chile-Argentina upper mantle. Because the anomaly above the central Chile–Argentina flat slab does not conform to known terrane boundaries but does align with the downgoing Juan Fernandez ridge track, we suggest that the orthopyroxene enrichment in this area may be related to flat slab processes, which would have implications for our understanding of lithospheric silica enrichment in the western U.S. and elsewhere.