os.fstat wouldn't work since it succeeds with non-"regular" files, e.g. standard I/O:
>>> os.fstat(0)
posix.stat_result(st_mode=8592, st_ino=5, st_dev=11, st_nlink=1, st_uid=500, st_gid=5, st_size=0, st_atime=1323629303, st_mtime=1323629303, st_ctime=1323628616)
I think the best solution is to call sendfile() and catch OSError, then fallback on the generic loop. However, you must also guard against fileno() failing:
>>> io.BytesIO().fileno()
Traceback (most recent call last):
File "<stdin>", line 1, in <module>
io.UnsupportedOperation: fileno