Manzardo is out of the lineup for Wednesday's game against the Mets.
Manzardo and fellow left-handed hitters Daniel Schneemann, Bo Naylor and Nolan Jones will head to the bench for the second time in the series while the Mets send southpaw David Peterson to the hill for the finale. David Fry will replace Manzardo as the Guardians' designated hitter and will bat cleanup.