Holmes quit the club suddenly on Thursday after more than three years in the role.
His final day will be Friday.
Chief financial officer Kevin Samson will take over on an interim basis, with Sharpless assisting.
Holmes is the third major pillar to fall in the past nine months after former coach Michael Voss' sacking last August and former chairman Angus Johnson's inglorious fall following an untidy boardroom split in October.
Holmes oversaw a tumultuous period at the Lions that continued to see the club lose money, but Sharpless was full of praise, saying he grew sponsorship and culture.
Sharpless met new AFL CEO Gillon McLachlan last week, but denied Holmes was pushed.
"We had been talking about his future here," Sharpless said at a press conference at the Gabba.
"Malcolm had a set term, he had an agenda of things he wanted to achieve, and I think Malcolm appreciated where the club is at the moment - he'd achieved a lot of things, and it was now time for him to move on."
Sharpless said the AFL had no involvement in Holmes' departure, and discussions on his tenure were purely between him and the board.
He said a search for Holmes' replacement would begin immediately, and denied talks with Carlton CEO Greg Swann were underway.
Sharpless said having "a football person" would help in the role.
"We don't expect it to be a quick process," he said. "We want the best person for the job."
Sharpless said he was confident of keeping his own position despite ongoing troubles securing finance for the proposed elite training and administration centre at Springfield, in Brisbane's west.
"The board's view is Springfield is the best option and the AFL's view is Springfield is the best option, but it may not happen. If it doesn't happen it doesn't happen.
"If we can't got to Springfield we stay at the Gabba and train at Coorparoo and give our player access to B-grade facilities."