Burnett (6-2, 1.89 ERA) is coming off the best outing of his resurgent season, yielding five hits over nine innings of Sunday's 1-0, 11-inning home win over Philadelphia.
It was the first time since 2012 that the 38-year-old pitched nine innings without allowing a run.
"Pitch efficiency all over the place," manager Clint Hurdle told MLB's official website.
Hurdle's club has a 0.69 ERA during its eight-game winning streak, part of a 21-5 stretch.
"He's still ahead of me?" Burnett told MLB's official website after his last start. "When you watch him do what he does, then I get to come out behind him, it's motivation. It makes me want to go a little more."
Burnett will get that chance as he tries to lead Pittsburgh (39-27) to its first nine-game winning streak since June 2013 in the opener of this three-game series.
The right-hander has gone 7-2 with a 2.21 ERA in his last 11 starts against Washington (34-33). He held the Nationals to one run over seven innings of a 3-1 win in his last outing at Nationals Park on Sept. 6.
He might not have to deal with Harper after the star outfielder fell in the wet outfield while making a throw Thursday and left with a strained left hamstring in Washington's 5-3 loss to Tampa Bay.
Harper is batting .344 with 22 home runs and 53 RBIs.
"Be smart about it, of course," said Harper, who will be evaluated Friday. "I want to be in there, but if I don't feel right tomorrow, then maybe taking that day off might help me a little bit."
Anthony Rendon went 7 for 16 with three home runs off Burnett last season, while Denard Span was 7 for 19 with two doubles. Span had two hits Thursday after missing one game due to back tightness and Yunel Escobar finished with his third five-hit game of the season.
The Nationals, however, have batted .205 while totaling eight runs during a four-game slide at home. They haven't lost five straight there since a six-game skid in July 2013.
Joe Ross (1-1, 3.46) looks to build on a strong second big-league start and help Washington avoid its eighth loss in nine home games. He allowed two runs and struck out eight over eight innings of Saturday's 7-2 victory at Milwaukee.
The right-hander will get his first look at the Pirates, who have continued to roll despite scoring three or fewer runs in nine of 11 games.
The Nationals have won the past four meetings.