They have received millions from the EU for research and new buildings.
The representative body Universities Wales says this funding ultimately has huge benefits for the Welsh economy.
But the Leave campaign say that universities and science would continue to get at least the same level of investment after Brexit.
The Remain camp say that is impossible to guarantee.
Some who want to leave also argue that the broader economic and democratic case for leaving, outweighs concerns about future funding for universities.
Earlier this month, Universities Wales published an open letter in which it outlined what it sees as the benefits of EU membership.
The letter, signed by the chair of the body, Cardiff University Vice Chancellor Colin Riordan, said the free movement of students and staff “enriches the student experience” but also made a contribution to the Welsh economy “worth hundreds of millions of pounds”.
It talked about partnerships with other EU researchers driving economic growth and innovation in areas such as healthcare.
It also points to the economic impact of EU students themselves, claiming it was worth more than £70m a year off campus in Wales.
Image captionSwansea University campus development received £95m of European funding
Swansea University’s Bay campus received £35m from the European Regional Development Fund and £60m from the European Investment Bank.
Swansea University’s Vice Chancellor has warned the university may have to downsize in the event of a vote to leave, potentially leading to job losses.
But a Cardiff University academic making the case to leave the EU argues that the money invested in Welsh universities is a diversion of the funds the British taxpayer contributes.
Kent Matthews, a professor of banking and finance at Cardiff University, says that outside the EU, universities like other institutions, would have to argue their case for the funding.
And he says “academic excellence is what generates funding”.
The quality of UK universities is also the key to attracting collaborators in other EU countries and across the world he said, rather than political structures.