Mortlock is still on the comeback trail from shoulder surgery, Gregan has retired while Larkham has moved to Japan.
The trio's non-availability would leave a gaping hole in any side in world rugby but Fisher is confident the Brumbies still possess a good mix of youth and experience.
"It's important to recognise while we have brought in several excellent young players into the squad, we've been fortunate enough to retain the vast majority of our side from last year," he said.
"If you look at players like Mortlock, (George) Smith, (Nic) Henderson, (Guy) Shepherdson, (Mark) Chisholm, (Gene) Fairbanks, (Mark) Gerrard, (Stephen) Hoiles, (Julian) Huxley, (Clyde) Rathbone and (Jone) Tawake, you have at least 10 or 12 players who've been playing at this level for at least four years.
"This is an exciting time for the squad as these players take on the senior roles within the team and establish their own identity while continuing the Brumbies' culture and traditions.
"We still have 11 Wallabies, seven Australia A representatives and nine players who were part of the squad when we won the Championship in 2004."
The Brumbies will hand debuts to four new recruits - Huia Edmonds, Mitch Chapman, Matt Toomua and Tyrone Smith - when they tackle NSW Waratahs in a trial match in Gosford on Friday night.
Chapman, a Queensland Red for three seasons, was glad to now be able to test his skills in the heat of competition rather than on the training track.
"Over the years the Brumbies' trial form has generally counted for little during the regular season and we see this as a good opportunity, particularly for a lot of the younger guys, to have a good hit out at this level before the season begins," he said.