The objective of the present study was to investigate the effects of substitution of soybean meal (SBM) and sunflower meal (SFM) with a mixture of whole white lupine seeds (WLS) and rapeseed meal (RSM) in lactation and growing diets on the milk yield and composition of rabbit does, as well as on the performance of their litters. Two lactation diets and two growing diets having identical ratios of digestible protein to digestible energy were formulated. The first lactation diet (SSL) contained 13.0% SBM and 5.0% SFM as the main crude protein (CP) sources, whereas the second lactation diet (RLL) was based on 10.0% RSM and 14.0% WLS. The first growing diet (SSG) included 7.0% SBM as the main CP source, whereas the second growing diet (RLG) diet was based on 6.0% RSM and 4.0% WLS. A total of 32 crossbred rabbit does (Hyplus PS 19 strain) were divided into 2 experimental treatments (16 each) and were fed one of the two lactation diets. All does were in the fourth parturition cycle. The litters (PS Hyplus 19×PS Hyplus 40) were standardized to 9 kits on the day of birth (Day 0). The litters were offered one of the two growing diets ad libitum from d 17 to d 33 (weaning) of age. At weaning, 10 litters/diet (a total of 90 animals of both sexes) were randomly chosen for the fattening period. Rabbits continued to be fed their respective growing diets ad libitum for 42 d. No significant differences were observed between treatments in terms of the body weight, feed intake or milk production of rabbit does during the entire lactation period. Interestingly, substituting the SSL diet with the RLL diet modified the fatty acid (FA) profile of milk fat; specifically, total n-3 polyunsaturated fatty acids (n-3PUFA) were significantly increased, thus tending to increase the total ratio of n-3PUFA to C20:4n-6 (P=0.067) in the milk of does fed the RLL diet. The RLL diet increased milk content of alpha-linolenic acid (P=0.037) and eicosapentaenoic acid (P=0.015). The performance of fattening rabbits was not affected by dietary treatments. It could be concluded that substitution of SBM and SFM with a mixture of WLS and RSM increased the milk content of n-3PUFA and had no adverse effects on the performance or milk yield of rabbit does or on the performance, carcass traits or viability of their litters.