Three puppies have been found dead in a weighted-down suitcase in the water, at the Port of Sunderland.
The "Staffordshire bull terrier type" dogs all had a severe skin condition and the RSPCA believes they were poisoned.
The dogs were aged between four and five months and are believed to be from the same litter.
Vets suspect the skin condition to be demodectic mange and that they may have been poisoned with rat poison.
RSPCA inspector Helen Bestwick said: "These puppies have suffered a great deal.
"They had blue staining on their bodies and around their bottoms and there were signs of vomiting.
"We don't know whether they were already dead when they went into the case, which was weighted down with two large stones.
"There were no scratch marks inside the case but it's possible they were too ill to struggle, or unconscious."