AWARE Wildlife Rescue is calling for help from the public following the deaths of at least four joeys and an adult female in Dawesville south of Mandurah, believed to be from poisoning.
Chief executive Sam De Hann said the animals had all died within a week near Sutherland Street and Melros Beach Road.
"Each has suffered a very slow painful death," she said.
"It is not clear at present whether the poisoning has occurred from toxic tree clippings placed on verges for collection or if it is from a chemical someone has sprayed on their garden not realising it would be toxic to kangaroos," Sam said.
She said it was an "unusual situation", but restricted to just a few streets in Dawesville.
"Many, many, many years ago we had a similar occurrence and thought that kangaroos had been eating a toxic plant," she said.
"This is something in that local area, we don't believe it's happening any further afield."
Testing is underway to determine the cause.
AWARE is working with Mandurah South Vets, Department of Biodiversity, Conservation and Attractions, including doing necropsies and sending away fluid and blood samples for analysis.
"We want to get a diagnosis of exactly what we are dealing with in the hope to prevents further deaths," Sam said.
"We are asking residents if you have recently sprayed for pests or placed clippings out on your verge where kangaroos forage, if you could contact us and let us know what chemical has been used or what species of plant you had placed outside that they showed interest in.
"If you are unsure but have seen kangaroos eating a particular plant, please take a photo of the plant and inform us of the location so we can take a sample and ID the plant."
Contact Sam 0499 900 630, Ros 0407 424 048 of Wendy 0403 240 388 if you have any information or further questions.