A key affordance of virtual reality is the capability of immersive VR to prompt spatial presence resulting from the stereoscopic lenses in the head-mounted display (HMD). We investigated the effect of a stereoscopic view of a game, Cellverse, on users’ perceived spatial presence, knowledge of cells, and learning in three levels of spatial knowledge: route, landmark, and survey knowledge. Fifty-one participants played the game using the same game controllers but with different views; 28 had a stereoscopic view (HMD), and 23 had a non-stereoscopic view (computer monitor). Participants explored a diseased cell for clues to diagnose the disease type and recommend a therapy. We gathered surveys, drawings, and spatial tasks conducted in the game environment to gauge learning. Participants’ spatial knowledge of the cell environment and knowledge of cell concepts improved after gameplay in both conditions. Spatial presence scores in the stereoscopic condition were higher than the non-stereoscopic condition with a large effect size; however, there was no significant difference in levels of spatial knowledge between the two groups. Most drawings showed a change in cell knowledge; yet some participants only changed in spatial knowledge of the cell, and some changed in both cell knowledge and spatial knowledge. Evidence suggests that a stereoscopic view has a significant effect on users’ experience of spatial presence, but that increased presence does not directly translate into spatial learning.