Mikhalkin improved his record to 20-1 with a convincing victory over the South African as judges carded 118-109 and 118-110 twice in favor of the Russian.
With the defeat, Oosthuizen drops to 27-1-2 and adds further misery to a period of ups and downs for the once Lou DiBella-signed fighter.
At cruiserweight, Mario Daser blasted out multi-time world title challenger Ola Afolabi after promising to do so pre-fight.13-0 TKO3
Weight issues for Afolabi prompted Daser to accuse the US-based Briton of not taking the contest seriously and it took the German just three rounds to get the job done.
Daser moves to 13-0 with a career-best win, whilst Afolabi is now 22-6-4 after being stopped in action for the very first time in his 30 bouts.
Christian Hammer carded a decision win over Zine Eddine Benmakhlouf on the bill to continue his good progress, whilst super-lightweight Fatih Keles and super-welterweight Sebastian Formella both celebrated wins.
Elsewhere in France, home favorite Thomas Masson picked up the vacant European Flyweight title with a ninth round stoppage of previously unbeaten Oleksandr Hryshchuk.
A crushing shot in the ninth saw Hryschuk complain of an injury to his face and the referee called off the contest to declare Masson the new champion.
Phil Jay is Editor of World Boxing News. Follow on Twitter @PhilDJay