The O's pulled off an upset in defeating Newport back in December, but have since sacked manager Ross Embleton. Jobi McAnuff has lost just one of his first four games in interim charge, and will look for his second away win since taking over.
Michael Flynn's Newport have won three of their last four, but slipped up against Port Vale during midweek.
Flynn will have new addition Joe Ledley available after the former Premier League footballer signed on Thursday.
Orient will be missing Adam Thompson, Louis Dennis, Ruel Sotiriou and Lee Angol.
Newport County: Townsend; Farquharson, Dolan, Demetriou, Shephard, Lewis, Labadie, Bennett, Sheehan, Amond, Taylor.
Leyton Orient: Vigouroux; Ling, Turley, Happe, Brophy, Cisse, Clay, Wilkinson, Kemp, Freeman, Johnson.
Ones to watch
The powerful wing-back has really come along leaps and bounds this season, touting himself as one of the most dangerous full-backs in the division.
26-year old Brophy has the highest average rating in the O's squad with a 7.06, and tops the assists chart with six. Brophy has also nabbed two goals from defence, but can saunter high up the pitch to act as a winger too.
Following his brace a few weeks ago to defeat Bradford City, Dolan has been in scintillating form of late.
Acting in centre-back, Dolan has the highest average rating of 7.0 and has notched three assists and six goals from defence, equal with the club's top scorer Padraig Amond. His free-kick specialty makes defenders terrified to foul him too.
As mentioned earlier, Leyton Orient came out on top in surprise fashion back in December, as goals from Brophy and Danny Johnson cancelled out Jamie Proctor's earlier opener to clinch a 2-1 victory.
How to watch
The match is available on iFollow via Newport or Leyton Orient's respective club websites, with match passes at £10 for those in the United Kingdom.