Why is reading one byte 20x slower than reading 2, 3, 4, … bytes from a file?

I was able to reproduce the issue with your code. However, I noticed the following: can you verify that the issue disappears if you replace

file.seek(randint(0, file.raw._blksize), 1)

with

file.seek(randint(0, file.raw._blksize), 0)

in setup? I think you might just run out of data at some point during reading 1 byte. Reading 2 bytes, 3 bytes and so on won’t have any data to read, so that’s why it’s much faster.