I am really getting frustrated with my truck.
I got two of the best tuners in the business trying to help me out but I need to see if anyone else has had similar issues.

My truck feels like a different truck every time I start it. Sometimes it feels sluggish and sometimes it feels like it have a lot of power.

This afternoon after talking to one of the tuners I got pissed off at it and I really put the pedal to the metal and at first it would not get above 2000 rpms and the it shoot right up to over 3000 and it became a different truck.

I had been averaging about 14.2mpg even on highway for about 260 miles and then just for the hell of it I reset the mpg and I got readings over 19.5 mpg and the it finally settled at about 17.6 on my 380hp setting.

My fuel pressure is good according to my monitor. The actual matches the desired. Got new air/fuel filter and cleaned the MAF.

What is making my truck feel lethargic most of the times and then I get a good drive out of it?

Any Ideas? Is it the EGR valve? Can I lose boost thru it?

Probably a bad tune/download?

Maybe, I guess I can reload the tune one more time but it has felt like this sluggish for a while

If it were me, I'd unload the tuner and go back to stock to see if the problem goes away with it. It could also be a faulty tuner, bad pin in the cable etc...

We don't generally see this on stock setup's...so...

I get sluggish response from time to time, and then it'll shift, then bang...away it goes...and in my case, I know it's something with the Banks and the Allison - like the adaptive tranny...just sayin'

These tuners are far from perfect.

Reloaded EFI with full flash just for the heck of it and now truck is running really good. 3rd time is the charm? I hope it stays there this time and not mess up again.
EGR blocker plate going in tomorrow....

Got the EGR plate installed but ran out of time and found out I got a boost leak. I am going to bring it back to my buddy on Tuesday to see what he can do about fixing the leak.
Even with the boost leak(I can hear whistle when O step on it and the Turbo Brake activates) I find the truck had more power and my DIC hit 21.5mpg and usually it is within a .1 or .2 of the hand calculated mpg. I don't want to get my hopes up but it seems like the EGR was the culprit to my mpgs and power issues. I do get a lot of black smoke now when I really put the pedal to the metal!

I'm about the same as you...except mileage is worse. Can feel like two or three different trucks when towing the fifth wheel. I'll get my plate on and try to check back in here.

With EGR turned off but not blocked combined with added boost can force it open. Happened in mine before I added the plate but the loss of power came when rpm and boost came up. I could actually hear a loud click when the gate was opened.

Got the truck EGR blocked and got the leak I was experiencing fixed. Now I am getting a P0401 code= Exhaust Gas Recirculation (EGR) Flow Insufficient.
Does this hurt my truck performance? I also keep getting P2033, P2455. P0546 codes and I get not CEL. I would think the truck would not run 100% when getting codes to safe guard against damage but been told that it did not matter getting these codes in background.

Disable ERG function with EFI and turn off reporting of any EGR related codes and you will be good to go.