Melancon, who is challenging Sen. David Vitter (R-La.), said his departure from the House Budget Committee had been coming.
"That decision was made several weeks back," he said on a conference call with reporters Thursday, "mainly because I didn't physically have the time." He said he "would have liked to have stayed," but his schedule didn't permit it.
He formally resigned from the committee Thursday.
Melancon is favored to win the Democratic nomination in the August primary but is expected to face a tough general-election campaign.
Louisiana Democratic officials claimed the party leadership pressured Melancon into leaving the committee for not supporting healthcare reform.
The conservative Blue Dog denied he was pressured to leave the committee because of his opposition to the healthcare bill. "No one has called me to threaten me," he said. The Democratic leadership "has not called my staff or myself to pressure us."
A spokesman for Speaker Nancy Pelosi (D-Calif.) said Melancon made the decision to leave the committee.
"Mr. Melancon is a valued member of the caucus. He made a decision to no longer serve on the Budget Committee. The Speaker respects his decision," the spokesman said.
The three-term lawmaker voted against the healthcare bill in November.
Melancon is opposed to passing healthcare reform via reconciliation.
"I don't want to go through the reconciliation process," he said, instead arguing for more targeted legislation. "Go back in, start from scratch," he suggested.
Robin Winchell, a spokeswoman for Melancon, said he "wants to devote more of his time and efforts to his work on the Energy and Commerce Committee, where he can more directly fight for Louisiana's thousands of workers and businesses in the oil-and-gas industry."
Vitter criticized Melancon's decision, saying he wanted to avoid tough committee votes.
Melancon "is quitting from the House Budget Committee so he won’t have to take tough votes on the huge Washington spending measures that Obama and Pelosi ask him to support,” Vitter said in a statement.
Vitter pointed to Melancon's departure from the House Science and Technology Committee last year as another example of him trying to "avoid the tough work."
"I’ve always charged ahead in advocating for Louisiana, while Charlie seems to prefer to run, hide and whine about all the partisanship in Washington as he simultaneously throws mud at me," he added.