The capital side rested several players, including striker Edin Dzeko and captain Daniele de Rossi despite being in a tight battle for the Champions League place for next year.
Francesco Vicari turned Lorenzo Pellegrini’s cross into his own net.
Radja Nainggolan smashed home from the edge of the box and Patrik Schick headed a third.
SPAL, who had drawn their previous six games are one point above the relegation zone – having played a game more than the teams below them. Roma, who go to Anfield on Tuesday for the first leg of their semi-final, are four points above fifth-placed Inter Milan, who have a game in hand.
As Roma who did the impossible over Spanish powerhouse Fc Barcelona by overturning a 4-1 deficit with a comfortable 3 nil win in Rome, will hope to replicate such form against Liverpool who smashed City 5-1
over two legs.