Butters has been sent for an arthroscope on a knee issue that "blew up" last weekend, coach Ken Hinkley says.
The brilliant on-baller will definitely miss Port's premiership season opener against Collingwood on March 15, but his status beyond that is unclear.
Butters, who has won Port's best and fairest award in the past two seasons, played against Adelaide in match simulation last Friday but reported problems the next day.
"Zak took a little knock to his knee a couple of weeks ago but it was nothing significant, nothing that we thought was any issue," Hinkley told AAP on Wednesday.
"It blew up over the weekend from no incident from the game on Friday.
"It's just one of those things that if you've got some issue going on inside, it doesn't expose itself almost immediately.
"In Zak's words, he was having no problems.
"He got through training and playing Friday last week no problems, but it just blew up on him."
He said Butters' status wouldn't be known until results from the arthroscope were received.
"We hope it's small, but we don't know," Hinkley said.
"We will give all that information out once we've got that information, and today we can't give you any more than that."
Backman Ratugolea pinched the medial meniscus cartilage in a knee at training on February 10.
The 26-year-old will miss Saturday's practice game against St Kilda, but is a chance to return in Port's internal trial on March 7.
"I would imagine there's an opportunity, potentially, for him to play some minutes in the internal trial ... but that's not a lock," Hinkley said.
"If there's any risk, we won't take that risk ... (but) we're optimistic around him being available somewhere very, very close to round one."
Fellow tall defender Brandon Zerk-Thatcher won't return until mid-May from a back injury suffered on February 5.
"It has been a really interesting pre-season for lots of clubs with injuries. There's a lot of injuries ... they're all quite different," Hinkley said.
"Zak's is an incident that we didn't even worry about, and then we have different types of things that have happened.
"Esava's was a pretty simple one at training, kicking, and Thatch's happened in the gym.
"So they're just rare injuries that our club is probably dealing with a little bit now.
"But what I do notice over the competition, there is a lot of injuries already, which can be really challenging for clubs."