First off, no, it has absolutely no effect on FE.

Secondly, almost no one who has a spare tire in their trunk keeps it inflated. That spare is useless to you unless it has 60 psi of air pressure in it. When it's low, it looks exactly the same as when it's not. When's the last time you checked yours?

Thirdly, you're better off carrying a battery jumper / air compressor "rescue pack". If for no other reason that to help someone else out. It's better than jumper cables in that you don't damage your own vehicle in the process.

Comments on the above:

• I've never had a spare tire that was underinflated to the point of uselessness, regardless of never checking inflation.
• I've had a few portable jumper packs, and they don't replace jumper cables, at least not for a big V8...maybe they're ok for a smaller engine. When fully charged, they're good when the car's battery has almost enough juice to do the job but not quite. Worth carrying, yes; worth replacing jumper cables, no.
• A big problem with them is keeping them charged. If I'm too lazy to check the inflation of my spare, what makes you think I'll bring it into my house once a week and plug it in?
• I've never managed to damage anything with jumper cables, and I've used them a million times, on modern computer controlled vehicles as well as old iron.
• Having an inflator/compressor is really great, and beats changing a low tire on the side of the highway or in the snow. Hook it up and sit in the warm driver's seat listening to the radio, then check on it once every five minutes. You can just pump it up to drive to the service station, or pump it up after plugging it with the plug kit I mentioned earlier (which is still quicker and easier than changing the tire IMO).

yea never understood not having it, i thought id be years before i got a flat... low and behold last year i was driving and trying to get up a steep hill and had the pedal floored and was dropping speed, shut off the radio listening for any weird engine noises, then kept hearing this whump whump whump noise and was like oh crap flat tire. pulled over indeed it was (all the way flat) got out the jack and lowered the spare and behold had it changed in 5 minutes and was on my way again.

if i didnt have it id either have to call one of my parents to get outa work to go home and get the spare (unlikely to happen, they woulda just said tough luck and call tow truck that woulda taken 30 minutes to get there) so i woulda been waiting around forever.

HC,

maybe one of us should put a message under our name or in our signature similar to theClencher's that says "Just leave the spare where it is dang it!"

My sig is full. My sig meta thread has the bit about weight FWIW.

I agree with HC about never having a spare lose pressure to the point of uselessness. I remember using the donut spare on my Pontiac wagon when it was 13 years old (It was never used before, and I doubt my dad ever checked it because you had to tear apart the car to get to it). @ 13 years the spare was still usable. Dad did keep one of those portable air compressors in the car too, so I guess if it was low I could have topped it off.

During the summer I carry a can of that inflat-a-tire repair stuff. but during winter I'll carry my (fully inflated;) ) spare tire and jack with me. I need the extra cargo space during the summer as I haul a bunch of stuff around.

lol that fix a flat crap is a pain, i know lots of tire places that the people working on them hate the crap. ive never had luck with it personally....

I was one of those tire monkeys that would complain about those fix-a-flat tires that would come in and need a new tire. But in a pinch, it works.

I like good fuel economy but don't want to take too much risk, so I carry the spare tire (fully inflated), the jack and the hand tools, and a pump in both of my cars. I feel good that some say that this bit of additional weight is not going to affect FE (significantly, I guess).
I believe that in many places, the law requires cars to have spare tires unless they have run flat tires.