Harry Maguire, Cristiano Ronaldo and Bruno Fernandes were amongst the stars sent abusive messages in the first five months of the 2021/22 season.
That is according to a report by Ofcom, with the Alan Turing Institute - the UK's national institute for data science and artificial intelligence.
United forwards Marcus Rashford, Jadon Sancho and Arsenal ace Bukayo Saka all felt the raft of supporters after missing penalties for England in the Euro 2020 final.
The study claims 2.3million tweets were sent in the direction of the trio.
It also found that a Premier League star was targeted every four minutes on social media platforms.
On average 362 abusive tweets were sent daily, with seven in ten Premier League players on Twitter abused. One in 12 tweets targeted race or gender.
United star Ronaldo was heckled the most, 12,520 tweets between August 12 2021 and January 24 2022, with the study finding 2.2 per cent were abusive.
Red Devils defender Maguire was second in line, picking up 8,954 abusive messages. Interestingly, 2,903 were sent on November 7 after the centre-back apologised to fans following the 2-0 defeat to Man City.
Rashford (2,557), Fernandes (2,464), Fred (1,924) and David De Gea (1,394) were also in the top ten - with departing midfielders Jesse Lingard (1,605) and Paul Pogba (1,446) seventh and ninth respectively.
England captain Harry Kane (2,127) also featured in the top ten, along with Man City midfielder Jack Grealish (1,538).
Ofcom is preparing to regulate tech companies under new Online Safety laws, which will introduce rules for sites, apps, search engines and messaging platforms aimed at protecting users.
The company's group director for broadcasting and online content Kevin Bakhurst said: "These findings shed light on a dark side to the beautiful game.
"Online abuse has no place in sport, nor in wider society, and tackling it requires a team effort.
"Social media firms needn't wait for new laws to make their sites and apps safer for users. When we become the regulator for online safety, tech companies will have to be really open about the steps they're taking to protect users. We will expect them to design their services with safety in mind.
"Supporters can also play a positive role in protecting the game they love. Our research shows the vast majority of online fans behave responsibly, and as the new season kicks off we're asking them to report unacceptable, abusive posts whenever they see them."
The Premier League is back and talkSPORT has it covered, with games on Friday, Saturday and Monday, beginning with Crystal Palace vs Arsenal on 5 August