Yes. Motherboards are considered major changes. Because if you replace the motherboard with a better one than the original manufacturer's part, you are effectivley creating a new computer and therefore, if your Windows license is an OEM license, would be in violation of the OEM license terms.
Simple really.
Edit to add :
Load Toad - If your motherboard is being replaced with the same manufacturer's part due to the previous one going faulty, then there shouldn't be an issue.