Six fire engines and around 40 firefighters were called to a fire at a bedsit above a shop on Rye Lane in Peckham.
A bedsit on the second floor was destroyed by the blaze and a small part of a third floor bedsit was damaged. One man and one woman left the building before the Brigade arrived. They were treated on scene for smoke inhalation by London Ambulance Service crews.
The Brigade's 999 Control Officers took 12 calls to the fire.
The Brigade was called at 1130 and the fire was under control by 1219. Fire crews from New Cross, Old Kent Road, Brixton, Croydon and Lambeth fire stations were at the scene.
The cause of the fire is under investigation by the Brigade and the Metropolitan Police Service.