Laryea Kingston, Michael Stewart, Jose Goncalves and Christian Nade will leave Hearts this summer as the club shed four of their highest-paid players.
And Australian winger Rocky Visconte has already returned to Brisbane Roar.
Stewart, stripped of the club captaincy recently, is in talks with Turkish Superleague outfit Genclerbirligi.
"Michael has moved on and it looks like Larry has moved on as well so that's a couple from the midfield we've lost," Jefferies told the club website.
Stewart's departure brings to a close his three-year spell with Hearts, with whom he had first spent time on loan while with Manchester United before joining Edinburgh rivals Hibernian.
Maybe another midfield player to take the place of Larry and Michael would be useful
Hearts manager Jim Jefferies
Portuguese defender Goncalves, who returned to Hearts this season after a year-long loan to Nuremberg, had not been chosen for the first-team since March.
Jefferies said that he would no longer pick the 24-year-old because he had rejected the offer of a new contract.
"Ryan Stevenson has done extremely well for us since he came in and he could be a big player for us next year," he added.
"We have Ian Black and Ruben Palazuelos but maybe another midfield player to take the place of Larry and Michael would be useful and we are certainly looking at a couple of options there.
"We are also looking at strikers and competition for places would be good."
Meanwhile, 25-year-old French striker Nade, who arrived at Tynecastle after leaving Sheffield United in 2007, has not played for Hearts since 10 April.
Kingston, who joined Hearts from Russian club Terek Grozny in 2007, had featured for the Edinburgh outfit in the latter part of the season after recovering from injury and had expressed his hope of being offered a new contract.
Goncalves and Nade have not played for Hearts for several months
The 29-year-old midfielder is presently training with Ghana's World Cup squad after being chosen in Milovan Rajevac's 30-man provisional squad.
Visconte had come through Hearts' youth system and played three times for the first team in January before being loaned out to First Division side Ayr United.
Meanwhile, Hearts have released striker Ryan Wallace and youth midfielders Elias Wagner and Billy McKenna.
Like Visconte, Wallace had made his first-team debut in January and made one more substitute appearance.
Austrian winger Wagner famously joined Hearts in 2007 only days after being released by neighbours Hibs as he was unhappy at his lack of games.
However, the 19-year-old, who suffered a double leg break last summer, failed to make the breakthrough at Tynecastle.
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