Midfielder Kalvin Phillips sealed a £42million move to Premier League champions Manchester City last week while Brazilian winger Raphinha arrived in Barcelona to tie up a transfer.
Despite the exits of the talismanic duo, Marsch is optimistic about the upcoming season describing the new campaign as one in which the club has the potential to grow.
The Whites have signed six players including big-money stars Luis Sinisterra and Brenden Aaronson.
But Marsch's optimism is not shared by O'Hara who has been unimpressed by the club's summer transfer dealings so far and believes Leeds could find themselves in trouble at the wrong end of the table.
"Leeds have lost Kalvin Phillips and Raphinha, They're in big trouble," O'Hara told talkSPORT.
"I know Leeds fans are gonna come on here and say 'no we're alright we're signing him and we're signing him'. They're signing nobodies."
O'Hara continued and made the bold prediction that Marsch would also be relieved of his managerial duties this season.
He said: "They're in big trouble, their two best players have gone, I think Jesse Marsch is gonna get the sack."
It remains to be seen how Leeds adapt to replacing their star duo with Raphinha registering 11 goals and three assists in his 36 appearances last season while Phillips played an instrumental role despite an injury-ravaged campaign.
In spite of O'Hara's disappointment in the club's transfer business, the Whites have flown out of the blocks in their attempts to bolster their squad ahead of the new season with Marsch raiding former club RB Salzburg for two of its stars.
USA international midfielder Aaronson and Danish defender Rasmus Kristensen both made the switch to Elland Road from the Austrian champions, whilst Marc Roca, Darko Gyabi, Tyler Adams and Sinisterra have all signed on at Elland Road.
Leeds have so far spent a staggering £95million on squad reinforcements with further additions in the pipeline.
They are currently on a pre-season tour of Australia and beat Brisbane Roar 2-1 on Thurday with goals from Daniel James and Joe Gelhardt.
They will now play two more games against more familiar opposition in Aston Villa and Crystal Palace.