I can understand power/fuel effecency loss if an engine gets too hot... affects compression and what not

What I have found was this...

For my first 3 hours of a drive, the MPGs I get is quite reasonable
If I stop for a few hours and then continue, same thing it's not bad

If I however continue driving (as I did yesterday for a 6 hours return trip)
The first 3 were fine, I then refueld, and tried again and I'd have to say was at the last 20-30% worse than the inital 3 hours

the engine temperature was fine (hovering below half as usual), and I seemed to have absolutely no power loss

Yesterday I checked my anti-freeze, and everything sat well in the tester
I changed my oil w/ more synthetic oil
I changed my air filter, sprayed down the throttle body with cleaner and pourd a gas treatment in

this is quite puzzleing

That's hard to explain, unless you were climbing hills on the second stretch.

nope... coming back the same way

Ah, I missed that inference.  Is the halfway point lower altitude than the start/ finish point?  If so, you went (on average) downhill outbound, and uphill on return.

If not, it has to be the wind.  Travelling with the wind outbound, and against it on the return.  Check with the weather service 

So many facters come into play. Ellevation, hill, ur right foot too. I use to notice the same when going back and forth on the same road