Protests swept the vast Oromia region and even reached the capital Addis Ababa, a rare event in a nation with a government considered among the most repressive in Africa.
"We have reports of between 48 to 50 protesters killed in Oromia. This death toll might be higher because there were a lot of wounded," said Merera Gudina, leader of the opposition Oromo People's Congress.
A diplomat confirmed 49 people were killed across Oromia, a region straddling central-western Ethiopia, and in Amhara, in the north.
The authorities have since Friday blocked access to social media, the activists' key channel for such rallying calls.