Inferring the structural connectivity from electrophysiological measurements is a fundamental challenge in systems neuroscience. Directed functional connectivity measures, such as the generalized partial directed coherence (GPDC), provide estimates of the causal influence between areas. However, the relation between causality estimates and structural connectivity is still not clear. We analyzed this problem by evaluating the effectiveness of GPDC to estimate the connectivity of a ground-truth, data-constrained computational model of a large-scale network model of the mouse cortex. The model contains 19 cortical areas composed of spiking neurons, with areas connected by long-range projections with weights obtained from a tract-tracing cortical connectome. We show that GPDC values provide a reasonable estimate of structural connectivity, with an average Pearson correlation over simulations of 0.74. Moreover, even in a typical electrophysiological recording scenario containing five areas, the mean correlation was above 0.6. These results suggest that it may be possible to empirically estimate structural connectivity from functional connectivity even when detailed whole-brain recordings are not achievable. Author Summary We analyzed the relationship between structural and directed functional connectivity by evaluating the effectiveness of generalized partial directed coherence (GPDC) to estimate the connectivity of a ground-truth, data-constrained computational model of a large-scale network model of the mouse cortex. We show that GPDC values provide a reasonable estimate of structural connectivity even in a typical electrophysiological recording scenario containing few areas. These results suggest that it may be possible to empirically estimate structural connectivity from functional connectivity even when detailed whole-brain recordings are not achievable.