Crystal Watts and Chelsea Hutt, both aged 15 from Blackbird Leys, were last seen on Thursday (28/3) at their home addresses.
Crystal is slim, around 5ft and has highlighted hair. Chelsea is around 5ft 5ins, with shoulder length dark brown hair. She was last seen wearing a black and white coat with a fur hood, a grey hooded jumper with a brown handbag and a coloured bag on her back.
Det Ch Insp Justin Fletcher, leading the search, said: “We are becoming increasingly concerned for the welfare of Crystal and Chelsea and are doing everything we can to try and locate them.
“We believe that the girls could have got a bus or train to Manchester, and are asking the public to contact us if they recognise the girls in the picture, or know where they might be.
“I would also like to appeal directly to Crystal and Chelsea to urge them to get in touch with their family or the police as soon as possible on 101.”
Alternatively, if you don’t want to speak to police or leave your name, call the charity Crimestoppers on 0800 555 111.