Sanford Health published a statement this week announcing it had 'mutually agreed to part ways' with longtime CEO Kelby Krabbenhoft.
Krabbenhoft leaving after 24 years in the position appeared after he sent an email to the company's 50,000 staff last week informing them he didn't need to wear a mask because he is immune to COVID-19.
'For me to wear a mask defies the efficacy and purpose of a mask and sends an untruthful message that I am susceptible to infection or could transmit it,' he wrote.
'I have no interest in using masks as a symbolic gesture.
'Masks have been a symbolic issue that frankly frustrates me,' Krabbenhoft wrote. 'The 'on-again, off-again' behavior of mask use by the general population violates every notion of serious infectious management that I was trained to adhere to, so some of this is absurd.'
He said he thinks that he is now immune to the virus for 'at least seven months and perhaps years to come' and that he isn't a threat to transmit it to anyone.'
The CDC encourages people to use masks because they help limit people who are infected - whether they know it or not - from spreading the virus.
It further says masks can also guard wearers who are not infected, though to a minor degree.
Sanford Health, which is based in South Dakota's Sioux Falls, has 46 hospitals and more than 200 clinics collected in South Dakota, North Dakota, Minnesota and Iowa. It hires about 50,000 people.
The Dakotas have for weeks had the country's highest spread rates of the virus.
The Midwest is now seeing the most cases and deaths per capita than any other area in the country.
Mask use has been a debatable issue in South Dakota with Republican Gov Kristi Noem denying a mandate or any COVID-19 similar limitations throughout the pandemic.
After Krabbenhoft's email last week, some Sanford executives quickly decided to distance themselves from the comments.
'Kelby Krabbenhoft's email was based on his own experience with Covid-19 and his personal opinions about the virus. They do not reflect the views of our health system as a whole,' Micah Aberson, Executive Vice President of Sanford Health, announced back then.
Dr Kathy Anderson, president of the North Dakota Chapter of the American Academy of Pediatrics, said it was 'an especially dangerous message to be sending right now in North Dakota.'
Krabbenhoft said in a statement that the timing of his departure was right for him and his family.
'We decided that today was a good time to retire,' he said. 'Sanford is in a good place, strongest ever.'