Defender Jean-Francois had been restricted to just one appearance for the Blades this season due to a long-standing knee problem that required surgery.
Teenage striker De Girolamo sustained his injury while playing for the Italy Under-18s against Austria earlier this month and has also gone under the knife.
Chesterfield-born De Girolamo, who has an Italian father, had been in contention for his first start for the Blades after making substitute appearances in home games against Colchester and Leyton Orient in February.
"Diego had his scan and underwent surgery straight away on a ruptured cruciate ligament," manager Danny Wilson told a press conference on Thursday.
"It will keep him sidelined for the long-term. We're certainly looking at a minimum of six months, which will mean he will miss the start of next season.
"The same goes for Lecsinel, who has had the same operation. During a scan it was discovered he had a ruptured cruciate, the same as Diego.
"It is a real blow for both lads and I can honestly say I am gutted for them.
"It isn't easy for anybody, but especially for a young lad who had all the excitement of the run-in in front of him.
"For Lecs, it just seems to be one thing after another, but as with Shaun (Miller), they will both have all our support and backing to get them back fit as soon as possible."