Your question has many possible answers. There are lots of factors. In general I would say there is a big difference between mp3 and lossless. Now if you are using tiny home theater in a box speakers, you may not notice much of a difference. The bitrate of the mp3 has an effect as well. As you increase the bitrate, the quality gets closer to lossless, but still falls short in most cases. That being said, I have heard some mp3 files (320) that I probably couldn't tell were compressed. I find this to be the exception rather than the rule. Quite a bit depends on the original file quality too. With the relatively low cost of hard drive space it makes sense to go lossless (at least to me).