Oddly enough, I had gained infamy from killing a lone NPC just yesterday when wiping out a faction, but a small number of NPCs are scripted to give infamy when killed under any circumstances, so I'm now assuming that was the case. But I guess that must be referring to dealing with multiple NPCs, though I don't recall ever seeing that specified. The single sneak attack rule is cited on the wiki and in tons of discussions, so I've always gone by that (and so have rarely been in situations that might disprove that).

You'll also find a copy of Guns and Bullets (on a desk), a reloading bench (in the back room), a dead prospector with some random loot (in the cell), and a Sunset Sarsaparilla Star Bottle Cap (on the ground next to the dead prospector). I then went into Doc Mitchell's house, who wasn't hostile, and again, killing him alone didn't give me infamy. At this location you'll encounter jackal gang members (inside and outside) and giant mantis nymphs (inside). But strangely, a couple people were hostile upon exiting the building, as if they had witnessed it, and killing them didn't give me infamy either for some reason. I then went to Goodsprings and killed Chet alone in open combat and didn't gain infamy. So it would seem that killing an NPC without witnesses does give infamy if multiple NPCs were engaged (i.e., only the initial assault/combat needs to be witnessed for the kill to grant infamy). I then killed everyone outside, and the last one out there gave me infamy as well. Like OP, I didn't gain infamy for killing a single NPC who was alone in another building. I notably gained infamy even for the last one I killed in there though, despite there being no one to witness it at that point.

I did gain NCR infamy for openly killing a group of quarry workers in the barracks (forgot Sloan uses NCR rep on the map, so that makes sense), and people outside didn't turn hostile, presumably because they didn't witness it. Yeah, I decided to do a little testing, and it seems I was almost entirely incorrect.

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