Around 2,000 Christmas Lego toy sets were stolen from the Fair Bricks charity, based in Huddersfield, overnight on Thursday.
The charity's toys were to be used by children in hospices and hospital over the festive period.
They were stolen from a vehicle, parked on a gated industrial estate off New Hey Road, Huddersfield.
It happened between 5pm on Thursday and 9am on Friday.
James Kitchen, Neighbourhood Policing Team Inspector for Huddersfield, said: “The items stolen were intended to help improve the wellbeing of children who may be in hospital, or hospices over the festive period.
“I would appeal to anyone to may have been in the area overnight who may have seen or heard anything suspicious or who has any information to come forward.
“I would also urge anyone who may see the sets advertised for sale via online auction sites or social media, or who is invited to buy them in person to think twice.
“These are not sets you would be able to ordinarily purchase and their availability to you may not be legitimate."
The sets stolen are set number 40222 - a 24-in-1 building set that was issued promotionally by Lego stores last Christmas.
They cannot be purchased in shops.
Insp Kitchen added: “If you are in doubt of the sets origin, don’t buy them, but contact the police.
“Our enquiries are very much on going to find those responsible.”
Anyone with any information is asked to contact police via 101, quoting 13170537540.
Information can also be passed to Crimestoppers on 0800 555 111.