Barry McCarthy has been ruled out of Tuesday's clash with Northern Knights at Comber.
The Pembroke seamer injured his knee in the first ODI against England last month and is continuing his recuperation.
Fiachra Tucker and skipper George Dockrell replace Gareth Delany and Andrew Balbirnie who are both in England for the T20 Blast.
Lightning secured a bonus point win in their home tie with Munster Reds, a clinical display which impressed Head Coach Nigel Jones.
“It was our objective to take five points from the game at Pembroke and it was very pleasing to do so," said Jones.
"It was a strong performance from the boys, but we’ve got to now build on that as we go to Comber to face the Knights.
“There will be different questions asked of us in tomorrow’s game and it is up to the boys to answer those questions by raising their performance levels again.
"They’re excited about the challenge though and we’re all looking forward to getting out there.”
The game is already a serious doubt given Storm Francis is set to hit Northern Ireland tomorrow, with heavy rain and gales forecast for Tuesday.