A growing number of social interactions are taking place virtually on video conferencing platforms. Here, we explore potential effects of virtual interactions on observed behavior, subjective experience, and neural "single-brain" and "inter-brain" activity via functional near-infrared spectroscopy (fNIRS) neuroimaging. We scanned a total of 72 participants (36 dyads) who engaged with their partner in three naturalistic tasks (i.e., problem-solving, creative-innovation, socio-emotional task), in either an in-person or virtual (Zoom) condition. We also coded cooperative behavior from audio recordings. We found increased and sustained prefrontal activation in the virtual condition, potentially providing a neural basis of "Zoom fatigue". We also observed reduced behavioral cooperation (i.e., conversational turn-taking), and altered patterns of averaged and dynamic inter-brain coherence, in virtual interactions. Inter-brain coherence patterns that were characteristic of the virtual condition were associated with reduced behavioral cooperation. These insights can inform the design and engineering of the next generation of video conferencing technology.