The animal charity said they were left without food, water or bedding in Ravenfield near Rotherham on January 10 at around 2pm.
Luckily, a member of the public spotted the pair and contacted the RSPCA for help and they were immediately brought to safety.
Animal Rescue Officer, Liz Braidley, who rescued the animals said: “These poor guinea pigs had been abandoned out in the cold and left inside a shoebox without food, water or bedding.
"The two male guinea pigs had possibly been fighting inside the confined space too as one of them had a bite mark on their ear.
“Thankfully, they were found when they were and we were able to take them to the RSPCA Leeds branch for some much-needed TLC (tender loving care).
“We are now appealing for anyone who might have any information about how these guinea pigs came to be abandoned to contact us on our inspectorate appeal line on 0300 123 8018.”
RSPCA said there were 1,478 reports of abandoned animals made to the charity in December - up 29 per cent on last year when the teams were called to reports of 1,049 abandoned animals during the same period.
Liz added: “We know that people’s circumstances can change which may mean they can no longer care for their pets but there is never an excuse to abandon them like this.
"We would urge anyone who is struggling to please reach out for help to friends and family, and charities like ourselves.”