Vaughan Gething said it was "incredibly frustrating to see direct lies" spread about a Gwent hospital on social media.
The health minister was speaking after a tweet spreading false claims about Nevill Hall Hospital, in Abergavenny, garnered more than 4,000 retweets.
Aneurin Bevan University Health Board came out to debunk the fake claims yesterday.
Referencing the situation today, Mr Gething said it was frustrating to see people not taking the situation facing the NHS seriously.
He said: "It is incredibly frustrating to see direct lies about what is taking place within our health service.
"Our health service is under significant pressure. Our staff can see what is already coming through their doors, both in primary care and in our hospitals.
"We need to take a step back and recognise the rising threat of coronavirus all around us.
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"The choice is what do we do to help keep all of us, our families and friends, safe.
"How do we do that, and how do we avoid getting into a position where we are harming the great national effort we are making.
"We need to do that so we can move safely into the future, and make sure that we lose as few lives and livelihoods as possible, over what is already an increasingly tough Autumn and Winter."
The tweet claimed that 200 of Nevill Hall Hospital's beds were unoccupied and that doctors could be found playing golf.
Both claims were debunked by the health board.
A spokesman for Aneurin Bevan University Health Board said: "Our hospitals are currently incredible busy and we can confirm that the information in this tweet is incorrect.
"Nevill Hall Hospital has 260 beds, which are fully utilised.
"One ward was closed last week for deep cleaning but this has now reopened."
The health minister also called on social media platforms, such as Twitter, to take more responsibility for the false claims that are spread on them.
Mr Gething added: "Some of this comes down to not just when the Welsh Government notice stuff, but it is actually the responsibility of people who run these social media platforms.
"They are doing more but we are not in a game here. We are in a really serious and significant position.
"So people who put false stories on to social media are the first point of taking responsibility, but the people who run those platforms and profit from them also need to have a measure and share of that."
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