Holders Balzan were knocked out of the FA Trophy, losing 3-1 to Mosta at the Hibernians Stadium.
Floriana are also out going down 3-1 to Santa Lucia and Sliema Wanderers went out to a late winner from St Andrews.
Valletta had to recover from a goal down to beat 10-men Gudja Utd while premier leaders Hamrun Spartans eased to a 3-1 win against Sannat Lions at the Gozo Stadium.
Tarxien Rainbows are through to the next round at the expense of Challenge League side Qormi.
Marsa edged out Zebbug Rangers and the all Challenge League tie between Naxxar Lions over Swieqi United ended in a comfortable 6-1 win for the Lions.
The tie between Hibernians and Zejtun was postponed.
