The four 15-second indents, which feature pupils from Eltham College in south east London, depict how a schoolboy's efforts to attract the opposite sex are thwarted by the embarrassing presence of a talking spot on his forehead.
Another four five-second idents will air from this week and run throughout the new series on Sky One, which has a predominately teenage following.
In one indent, entitled "just wondering", we see the unfortunate schoolboy trying to ask a girl out. But before he can get the words out his spot shouts: "You really want me, don't you?"
In another execution, a pretty girl asks to sit down next to him. The spot jumps in with another inappropriate comment: "Do I look desperate? You truffle-hunting swamp donkey."
All four versions end with the voiceover stating: "Don't let spots ruin your chances."
John Parton, the group brand manager at GlaxoSmithKline, said: "Malcolm in the Middle is one of the most popular teenage drama series on Sky One, following the trials and tribulations of a young teenager, his family and friends. This, coupled with its irreverent humour makes it a perfect match for the Oxy brand."
The campaign was written by Jim Ritchie and art directed by Chris Hart. The director was Morgan Hutchins, with production through The Mob. Media was handled by MediaCom.