"The European Union is a union of 27 member states. The UK is only one country. And we have a population and a market of 450 million people," he told the BBC on Sunday, adding that the EU could take the upper hand in negotiations, citing the two sides' vastly different populations.
"The UK, it's about 60 (million). So if these were two teams up against each other playing football, who do you think has the stronger team?"
Varadkar, who is is due to meet the EU's chief negotiator Michel Barnier in Dublin, also questioned the timetable set by Prime Minister Boris Johnson to get a trade deal with the rest of the EU by the end of the year.
He disagreed with Johnson's claim that there is "bags of time" to sign an agreement, warning "it will be difficult to do this".
The Prime Minister told the BBC that there might have to be an extension to the next phase of the Brexit process, beyond the end of this year, to finalise a trade deal.
However, he vowed to work "night and day" to try and get it done, saying: "We won't be dragging our feet."
Varadkar, the lead of the Fine Gael party, will fight his first election campaign as Prime Minister when Ireland will heads to the polls on February 8.
The UK is set to leave the EU at 11 p.m. on Friday, marking an end to the 46 years of the country in the bloc.
The UK has agreed to abide by EU rules during a transition period until the end of the year.
By 2021, the UK aims to have agreed a deal on future ties.
( With inputs from IANS )