Electrical stimulation of the hypoglossal (XII) nerve has been demonstrated as an effective approach to treating obstructive sleep apnea (OSA) The physiological effects of conventional modes of stimulation (i.e., genioglossus activation or whole XII nerve stimulation), however, have yielded inconsistent and only partial alleviations of hypopneic or apneic events. While selective stimulation of the multi-fasciculated XII nerve offers many stimulus options, it is not clear how these will functionally affect the upper airway (UAW). To study these effects, animal experiments in eight beagles were performed to investigate changes in the UAW resistance (R_UAW) and critical pressure (P_crit), during simulated expiration (n = 4) and inspiration (n = 4). During expiration, non-selective XII nerve stimulation yielded the greatest improvement in R_UAW (-0.66 ± 0.11 cmH₂O/L/min), compared to that for selective activation of the geniohyoid (GH; -0.29 ± 0.09 cmH₂O/L/min), genioglossus (GG; -0.31 ± 0.12 cmH₂O/L/min) and hyoglossus/styloglossus (HG/SG: 0.37 ± 0.06 cmH₂O/L/min) muscles. For simulated inspiration, on the other hand, only whole XII nerve stimulation (-0.9 ± 0.4 cmH₂O) and co-activation of the GG + HG/SG muscles (-1.18 ± 0.6 cmH₂O) produced significant (p < 0.05) improvements in UAW stability (i.e., lowered P_crit), compared to baseline (-0.52 ± 0.32 cmH₂O). The results of this study suggest that a multi-contact nerve electrode can be used to achieve both UAW dilation and patency, comparable to that obtained with non-selective stimulation, by selectively activating the various branches of the XII nerve.