May 3rd marks 14 years since Madeleine, from Rothley, disappeared from an apartment in Praia da Luz, in the Algarve region of Portugal.
She was just three when she went missing in as yet unsolved circumstances in 2007.
Kate and Gerry McCann said the COVID pandemic had made this year "even more difficult for many reasons" and the investigation to find Madeleine and her abductor is ongoing.
The statement from Kate and Gerry McCann said: "Every May is tough – a reminder of years passed, of years together lost, or stolen. This year it is particularly poignant as we should be celebrating Madeleine’s 18th birthday. Enough said.
"The Covid pandemic has made this year even more difficult for many reasons but thankfully the investigation to find Madeleine and her abductor has continued.
"We hang on to the hope, however small, that we will see Madeleine again. As we have said repeatedly, we need to know what has happened to our lovely daughter, no matter what. We are very grateful to the police for their continued efforts.
"We still receive so many positive words and good wishes despite the years that have gone by. It all helps and for that we are truly grateful – thank you.
A German man known as Christian B, due to the country's strict privacy laws, was identified last year as a suspect in Madeleine's disappearance.
He was convicted in 2019 of the rape of a 72-year-old woman in Portugal in 2005 at the same seaside town where Madeleine went missing.
His appeal against the rape conviction was thrown out of court in November.