This followed the testing of players and staff ahead of a return to training.
“The Premier League can today confirm that, on Sunday 17 May and Monday 18 May, 748 players and club staff were tested for COVID-19,” the league said in a statement.
“Of these, six have tested positive from three clubs.”
No details were released over which individuals or clubs are affected.
“Players or club staff who have tested positive will now self-isolate for a period of seven days,” added the league’s statement.
Brighton have previously confirmed three positive cases among their squad at different stages of the pandemic, while positive tests for Arsenal manager Mikel Arteta and Chelsea winger Callum Hudson-Odoi played a major role in the decision to suspend matches on March 13.
Premier League clubs began returning to training in small groups on Tuesday after protocols on safety measures were signed off on Monday.
The number of positive cases represents just 0.8 percent of those tested and is consistent with similar widespread testing conducted by other major leagues hoping to complete the season.
Germany’s top two divisions registered 10 positive cases out of 1,724 tests two weeks ago ahead of their return to action last weekend.
Five players from Spain’s top two divisions tested positive last week before La Liga’s return to group training.
Premier League clubs are aiming for a return to action by the middle of next month, but face resistance from players concerns over their welfare.
Watford captain Troy Deeney has said he will not return to training this week due to fears he could pass the virus on to his five-month-old son.
“I can’t get a haircut until mid-July, but I can go and get in a box with 19 people and jump for a header,” said Deeney on the Talk The Talk podcast.
“I don’t know how that works. No one could answer the questions, not because they didn’t want to, but because they don’t know the information.”
Newcastle left-back Danny Rose claimed players were being treated like “guinea pigs or lab rats”.
Rose’s manager Steve Bruce said the majority of his players are in favour of a return to training and praised “meticulous” planning on behalf of the Premier League to make the environment as safe as possible.
However, Bruce has also questioned the limited preparation time players could have between returning to contact training and competitive matches, warning his squad could “fall down like a pack of cards” with injuries.