You didn’t mention the age of your son, which makes it difficult to recommend specific activities. So I will comment on types of activities. I’m sure you can adjust the suggestions to your son’s maturity level.
First, keep in mind how many opportunities there are in everyday living to teach spatial relations. Big/little, up/down, left/right, above/under (or below), in/out are all examples of spatial relations.
I am a strong advocate of having parents occasionally play with their children rather than merely supervising their play. Let’s say you’re playing with cars and trucks. Maybe begin by laying down a road with blocks. Keep up a steady stream of conversation. “What shape is the road (oval, round, rectangular)?)” “Hey, you’re on the left side; cars drive on the right side of the road.” If he forgets, let a little “accident” occur to help reinforce the left/right idea. Maybe you’ve made a bridge. Comment that boats go under it and cars go over it. Use a box for a garage and ask him to put his car in the garage or maybe to take it out. If he sets the table, remind him that napkins and forks go on the left and knives and spoons on the right. (And you’re teaching him table etiquette as well as spatial relations.) Comment as you get in or out of the car, that you are in the front seat and he is in the back. Break a cookie slightly unevenly and ask him which piece he wants. As you know, he will choose the bigger piece, giving you an opening to comment, “Oh, you took the big piece. Well, I’ll eat the little one.” I’m sure this is enough to get the idea across.
There are many toys that can help. As you indicate, puzzles are great. Make certain you don’t buy those that are too difficult for him. If he’s already a little weak in this area, they will just frustrate him. And mazes are great. Most coloring books (which some people deplore) contain several. Finally I would suggest that exercise and dance can improve a child’s sense of spatial relations.
Our parenting advice is given as suggestions only. We recommend you also consult your healthcare provider, and urge you to contact them immediately if your question is urgent or about a medical condition.