Both will be assessed this week, with Sandilands suffering glute tightness and Mayne catching his right ankle under the leg of Cats' opponent Joel Hamling when tackled across the boundary line in the second half at Patersons Stadium.
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Mayne, who was reappointed to the club's leadership group during the week, spent some time lying on the ground in agony before being helped off the field aided by trainers.
The 24-year-old was walking in the changerooms after the incident and Lyon was positive the runner-up club champion had escaped serious injury.
Eagles claim early bragging rights
"We're pretty confident it's a ligament in the ankle and he'll be running within seven days," Lyon said.
"Obviously we need to check that off with a scan.
"It didn't look good. I felt a little sick in the box, obviously when you see one of your players get hurt.
"Aaron (Sandilands) just tightened up, a bit of a glute. We'll check that out as well.
"It's not perfect, but it doesn't seem on the surface anything too [serious]."
The injuries were the only sour point in an otherwise impressive start to the NAB Cup by the home side, who were led to the 7.6 (48) to 4.6 (30) victory by prolific midfielder Michael Barlow.
Barlow showed he could push to join the game's elite midfielders with 15 disposals, three clearances and two inside-50 entries in the shortened match.
Without a number of its stars heading into the fixture, including captain Matthew Pavlich, David Mundy and Nat Fyfe, the club was intent to use the early stage of the pre-season competition to expose some younger players.
And Lyon would have seen some encouraging signs, with midfielders Cameron Sutcliffe and Tom Sheridan covering the ground nicely, and Michael Walters adding some class close to goal.
After coming from behind to beat West Coast in the opening game of the night, the Cats started slowly against Freo, conceding four of the first five goals.
But a comeback in the second half, spearheaded by two goals to 22-year-old forward Mitch Brown, put them back in the contest before Fremantle kicked the final two goals to win comfortably.
After his match-winning supergoal against the Eagles, Cats captain Joel Selwood was the most impressive Cat, collecting seven disposals and booting two goals.
Super Selwood leads Cats past Eagles
The loss could be costly for the Cats, with star midfielder Steve Johnson likely to come under scrutiny for contact made with Fremantle's Hayden Ballantyne.
Johnson's 'love-tap' to Ballantyne's midriff did not appear to be of serious force, but did leave the Fremantle small forward hunched over for several moments.
There is history between Ballantyne and the Cats after a spiteful round one meeting last year, which saw Geelong defender Matthew Scarlett suspended for three weeks for striking him.
Ballantyne was also suspended for two weeks for striking Cats veteran Paul Chapman in the same match.
WHAT THE COACHES SAID
Fremantle coach Ross Lyon: "Our speed and intensity was evident against Geelong early and then they gathered themselves at the break and came again at us. We turned it over in our [defensive] 50 in a manner that we haven't in a long time. I think it's quite easily fixed, so that doesn't concern me too much, but it's a good reminder of where you can get into trouble in the modern game."
Geelong coach Chris Scott: "We got some quality game time into most of our list. Chapman, Mackie and Kelly were the only notables that were available that we didn't bring with us. I think that's a good thing this year compared to last."
It's hard to go past Joel Selwood (MID, $530,900). Selwood grabbed 48 Dream Team points against Fremantle and only had seven disposals, showing he can score even when he doesn't have the ball. Sixteen of those points came through tackles, a big part of Selwood's make-up as an AFL Fantasy option.
FREMANTLE 0.4.2 0.7.6 (48)
GEELONG 0.2.4 0.4.6 (30)
Fremantle: Walters 2, Crozier, Mayne, Mzungu, C.Pearce, Silvagni
Geelong: Selwood 2, Brown 2
Fremantle: Barlow, Walters, C. Pearce, D. Pearce, Sutcliffe
Geelong: Selwood, Brown, Duncan, Johnson
Fremantle: Mayne (right ankle)
Official crowd: 21,804 at Patersons Stadium