Pence had started his Saturday by tweeting a photo of himself and his wife Karen, decked out in their Colts gear, and ready to take in the game, in which former Colts quarterback Peyton Manning was being honored.
Pence is a known Colts fan, having served as an Indiana congressman and then governor of the Hoosier State.
Things quickly soured for the Pences before kick-off, as Colts players stood arm and arm and several 49er kneeled during the playing of the Star Spangled Banner.
It should have been no surprise to Pence that the teammates of Colin Kaepernick - who played for the 49ers last year when he started taking a knee to protest racial injustice - would have done the same today.
Taking the mantel from Kaepernick, who's currently a free agent, some San Francisco players have taken a knee at every game this season.
But Pence still got offended and tweeted in disgust.
The White House's statement echoed his tweets.
'At a time when so many Americans are inspiring our nation with their courage, resolve, and resilience, now, more than ever, we should rally around our Flag and everything that unites us,' Pence argued.
'While everyone is entitled to their own opinions, I don't think it's too much to ask NFL players to respect the Flag and our National Anthem,' he continued.
'I stand with President Trump, I stand with our soldiers, and I will always stand for our Flag and our National Anthem,' he said.
The vice president later tweeted a photo of himself standing, with right hand over heart, for the Star Spangled Banner.
'We were proud to stand - with all our @Colts - or our soldiers, our flag, and our National Anthem,' Pence wrote.
Prepared for the renewed controversy, the White House's press shop quickly pushed out that exact photo to reporters as well.
'Vice President Mike Pence, Second Lady Karen Pence, and Major General Courtney P. Carr stand for the singing of the National Anthem at Lucas Oil Stadium before the start of the Indianapolis Colts game against the San Francisco 49ers prior to leaving the game on Sunday, October 8, 2017,' the White House captioned the image.
President Trump was visiting Huntsville, Alabama on September 22 when he loudly inserted himself in the kneeling debate by calling out players who engaged in the protest, which was supposed call attention to continued racial inequality in the country.
Conservative have instead suggested those players protesting are insulting the American flag, veterans and the armed forces.
Trump said he thought it would be great if an NFL owner responded to a player kneeling by saying, 'Get that son of a b***h off the field right now, out, he's fired. He's fired!'
The president briefly turned his attention to another sport when Golden State Warriors player Steph Curry suggested his team could 'inspire some change' by refusing Trump's invitation to the White House to celebrate an NBA playoffs win.
'Going to the White House is considered a great honor for a championship team,' Trump wrote Saturday morning. 'Stephen Curry is hesitating, therefore invitation is withdrawn!'
At the same time, Trump continued to hammer the issue, suggesting at one point that the NFL should ban players from taking the knee.
All the while, U.S. territory Puerto Rico was being ravaged by Hurricane Maria.
Journalists questioned whether the NFL controversy had distracted the president from being fully engaged in the storm, which has left the island decimated.
'I wasn't preoccupied with the NFL,' Trump said at a Rose Garden presser with Spanish Prime Minister Mariano Rajoy on September 26. 'I was ashamed of what was taking place.'
Trump made a trip to Puerto Rico this week to survey storm damage and took heat after he joyfully threw paper towel rolls at hurricane victims.
In an interview that aired Saturday night with former Arkansas Gov. Mike Huckabee, the father of Trump's Press Secretary Sarah Huckabee Sanders, the president characterized the PR blunder as 'fake news.'
'They had these beautiful, soft towels, very good towels,' Trump explained, noting the crowd was 'loving everything' and 'having fun' as Puerto Ricans gathered waited to pick up supplies.
'They said, "Throw 'em to me! Throw 'em to me, Mr. President! ... the cheering, it was deafening,' Trump said, and then placed the blame on the media for critics calling the move disrespectful.
'They turned down the sound,' he said, suggesting networks had muted the audience's positive reaction.
-More to come