The four - Anne McTaggart, Hanzala Malik, Siobhan McMahon and Dave Stewart - are in the sights of party members who want new blood in the Parliament.
Labour's defeat at the last Holyrood election saw well-known MSPs lose their seats and a host of unfamiliar faces elected on the regional Lists.
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Some of the List members are highly regarded but others are considered surplus to requirements.
Labour's re-selection rules protect existing List MSPs, which means that subject to passing a trigger ballot no party member can come above them in the rankings.
A proposal to scrap protected places, which would allow any party member to top a regional List, was scrapped after objections from sitting MSPs and trade unions.
However, reforms were pushed through earlier this year that gave party members more say in each List MSP's trigger ballot.
If a List member fails to win the approval of more than 50% of party members, he loses his protected place on the List.
Senior party insiders have told this newspaper that activists are targeting several sitting members who will face a trigger ballot after the referendum.
Malik and McTaggart, both former councillors, are MSPs on the Glasgow List.
McTaggart recently failed to win a selection for a Labour constituency seat.
McMahon is a Central Scotland MSP and Stewart is a member in the Highlands and Islands.
Stewart, a former MP, is said to have been strongly opposed to the move to scrap protected places.
A Labour insider said there would be "concerted effort" in the case of the four MSPs. "There is no objective justification for protected places on the List," the insider said. "None of them bring any incumbency advantage. How many voters know who their List MSPs are?"
The source added: "How could someone who's spent most of the past 17 years in the House of Commons and Holyrood have a profile as low as Dave Stewart?
"And Hanzala and Anne would never have made it through the local government panel for Glasgow in 2012.
"It's absurd that they're safer in their job as MSPs than they were as councillors."
SNP MSP Sandra White said: "This apparent attempt to unseat sitting Labour MSPs comes amid persistent rumblings of discontent over Johann Lamont's leadership.
"It seems that yet again civil war is brewing in the ranks of the Labour Party.
"These latest moves will only increase the pressure on Johann Lamont to get a grip of her party before it is too late for her."
McTaggart said: "It is not appropriate for me to comment on internal Labour Party matters and selections."
The other MSPs did not respond to a request for comment.
A Scottish Labour spokesperson said: "We have an open and transparent selection procedure which empowers our party members to select the candidate they feel will best represent their communities."