The Spotless is a term used by Monokuma during the Killing School Life/Killing School Trip in Danganronpa: Trigger Happy Havoc and Danganronpa 2: Goodbye Despair. During a Class Trial, they are the students who have not committed a murder and they oppose the blackened student who has committed a murder and are attempting to use the Class Trial to escape.
Danganronpa and Danganronpa 2
The Spotless are all students who haven't committed a murder when participating in a Class Trial. The term was first used by Monokuma in Danganronpa: Trigger Happy Havoc after the murder of Sayaka Maizono, but immediately introduced after Monokuma's appearance in Danganronpa 2: Goodbye Despair, both during Monokuma's explanation of the Class Trial.
If the Spotless are able to determine the Blackened during the Class Trial, then only the Blackened student is Executed. However, if they pick the wrong culprit (another Spotless), then all the Spotless are executed and the Blackened can leave the School/Island.
In Chapter 1 of Danganronpa, it was revealed that an accomplice to a murder does not get to graduate, thus being spotless themselves.
In Chapter 3 of Danganronpa, it was suggested that if two murders occur by separate people, then both become the Blackened and it does not count as a murder.
In Chapter 5 of Danganronpa, even though Kyoko Kirigiri/Makoto Naegi were not the true Blackened, due to the Mastermind attempting to get rid of Kyoko, the Spotless were not executed and Kyoko/Makoto was executed/attempted executed instead.