Introduction Experimental litter size manipulations are often not problem free. Typically conducted shortly after birth or oviposition, they do not account for the energy already invested into the production of the offspring. Such effects make it difficult to interpret the results from experimental litter size manipulations and therefore to study optimality of litter or clutch size, a long debated topic in evolutionary biology. Results We propose the use of a mating design based on a selfish genetic element, the t haplotype, to reduce litter size in an eutherian mammal, the house mouse. Most t haplotypes are recessive lethal and therefore lead to the death of all homozygous embryos. Litter sizes can be reduced by up to 50% by pairing a +/t female with a +/t male instead of a +/+ male. Conclusions This method allows litter size manipulation before birth without the use of invasive techniques, therefore providing an excellent tool for studying optimal litter size and ultimately helping to understand life history strategies.