Brighton are currently just one place outside of the Sky Bet Championship play-offs in seventh, but the south coast club have lost Barnes to Burnley, with Bridcutt linked with Sunderland.
While disappointed by the departures, Mackail-Smith does not begrudge either player the chance to play in the Premier League, with Burnley currently in the second automatic promotion place at the top of the Sky Bet Championship.
He told Sky Sports News Radio's Football League Hour: "Ashley Barnes will be a big loss for us because he's been fantastic, but he's joining Burnley and will be a fantastic signing for them.
"Liam Bridcutt has been in the papers as well being linked to Sunderland. He's a fantastic player and it'd be difficult to lose someone of his quality but obviously if a Premier League club comes calling you have to say 'go and prove yourself at that level'.
"It's disappointing for us because we all want to play in the Premier League but if the opportunity arises for players, we want to see our team-mates go on and have the opportunity to perform at the highest level."
He added: "They're both very young so they've still got a lot to learn but they've done well at Brighton, proved themselves in the Championship, and if they've got that opportunity to go to the Premier League then they can't turn that down.
"Then it's up to them, how much dedication, how much effort, how much belief they have in themselves that they can play at that level."
Mackail-Smith also provided an update on his fitness as he continues his comeback from an Achilles injury, while the 29-year-old also joins former Leicester and Derby striker Ian Ormondroyd and former Sheffield United defender Rob Scott in making their predictions ahead of Friday night's big East Midlands derby in the Sky Bet Championship.
Wolves captain Sam Ricketts, Preston striker Kevin Davies, Northampton midfielder Darren Carter and Plymouth defender Guy Branston are also on this week's show.
Listen to the full Football League Hour Podcast here or via the Soundcloud player below.