"What is everybody upset about?" Landrieu asked from the Senate floor on Tuesday. "We already have 2.6 million miles of pipe in America." She noted that the Keystone project would add "basically 1,000 miles."
Landrieu, who faces a runoff against Republican Rep. Bill Cassidy in her home state Dec. 6, has fought to make the issue a top priority during the lame-duck congressional session. However, critics see her efforts as a last-minute attempt to win over voters in Louisiana, where the bill has gained public support.
Read MorePrivate equity bets on 'revolution'—in oil and gas
The House passed Cassidy's version of the bill on Friday.
Earlier in the year, the State Department concluded that the project would create 42,100 jobs and about $2 billion in earnings throughout the country. However, it defined those jobs as lasting for about a year.
Proponents of the construction argue it would help the U.S., which still imports about 30 percent of its oil supply, move away from relying on energy sources in unstable areas of the world. However, environmental activist who oppose the pipeline say it would jeopardize public health and spike carbon emissions.
The White House has indicated that President Barack Obama would veto the bill if it passed.
Read MoreCracks widen at OPEC as oil prices tumble