old66tiger

Fired up the new LS3 Saturday with open headers and the idle was choppybut it ran with no MIL codes. Ran only for 20 seconds or so and then shut off. I may have fired it up 2-3 more times that day but with open headers it was loud and I was more interested in getting exhaust on. Fast forward to Monday and we loaded it on the trailer to head to the exhaust guy. It quit on me a few times and started hard. It was at that time it popped a MIL. We got it to the exhaust shop and got the exhaust hooked up. When we loaded and unloaded it, it ran rough and MIL came on again. When I got it home the code came up as a P0300. Multiple cylinder misfire. Pulled plugs last night and they were black. Cleaned them up and when the new wires come today, I am going to throw it back together.

So...the assumption here is that he open headers caused a O2 rich condition, popped a P0300 code and resulted in fouled the plugs. Then, with exhaust on it, the fouled plugs caused another P0300 code. Sound plausible? Anything else I need to check? Possible that I washed down the cylinders?

mrvedit

I'm no expert, barely a novice with helping people here, but it sounds plausible to me. Open headers will allow ambient air to register as a very lean condition, causing the LTFT to enrichen to the max, fouling the plugs.
A good scanner can reset the LTFT. Perhaps there are other ways too. (Disconnecting the battery for a while?) I wouldn't run it again until the LTFT is reset.

Are you sure your tune is correct for the new engine?