Yeah, I mean, there are whole episodes or large segments of episodes where he doesn't even try to really be funny at all, but rather just gives you a slice of life incident that you can relate to or sympathize with.
For instance, the episode where he was on a date and a bunch of high school punks were being disruptive in the diner, and he asked them to please keep it down a bit, so they got pissed and the largest of them (they were all jocks) confronted Louie and threatened to beat him up. Being reasonable and not wanting to fight or get arrested, he backed down, and then the date judged him negatively for not fighting. It was just a sad, no-win scenario that most people can understand even if they haven't experienced that exact situation (but they've likely experienced something similar or something that could have turned out that way).
Or the episode where he pours his heart out to his best friend and she --while thinking he's a great friend-- does not return his love in the slightest. That was more heartbreaking then funny, even though they occasionally said humorous things.
The show doesn't back away from being sad, vulnerable, awkward, and often brutal at times, and that's what makes it more honest and appealing in my mind than most shows on TV.