Abstract Sows were supplemented with high dietary zinc (Zn) at different times in gestation to determine effects on piglet tissue mineral concentrations and gene expression. Ten sows per treatment were assigned to dietary treatments: 1) Control—sows fed a corn–soybean meal-based diet containing 206 ppm total supplemental zinc supplied by zinc hydroxychloride from mating to farrowing; 2) Breed-to-Farrow—as Control + additional 147 ppm supplemental Zn as ZnSO4 fed from 5 d post-breeding to farrowing; and 3) Day 110-to-Farrow—as Control + additional 4,079 ppm supplemental Zn as ZnSO4 starting on day 110 of gestation until farrowing. Final supplemental Zn concentrations of the Control, Breed-to-Farrow, and Day 110-to-Farrow treatments were 206, 353, and 4,285 ppm, respectively. Serum, colostrum, and milk were collected from each sow. At farrowing, 2 average birth weight (ABW) and 2 low birth weight (LBW) piglets from each sow were selected for collection of serum and tail samples within 2 d of birth. Liver tissue was collected from 65 piglets that died naturally (n = 35) or were euthanized (n = 30). Blood was collected from a different group of piglets (9 LBW piglets per treatment and 8 ABW Control piglets) for RNA-sequencing to evaluate differentially expressed genes (DEGs) and pathways. Mineral concentration data were analyzed using a generalized linear mixed model and RNAseq data were analyzed using the edgeR program. Diet did not affect mineral concentrations of sow serum, colostrum, and milk (P > 0.05). Mineral concentrations of piglet serum were not influenced by maternal Zn treatment or piglet birth weight. Tail Cu for LBW piglets born to sows fed high Zn tended to be lower than Control piglets (P = 0.082) while piglets of LBW had greater concentrations of Fe (P = 0.018) and Cu (P = 0.031) in tails compared to ABW piglets. Piglets that died naturally had greater hepatic Fe concentrations (P < 0.001) than healthy euthanized piglets. Only 2 to 3 DEGs were noted between Control LBW and LBW piglets born to sows fed high Zn. However, 262 DEGs were identified between LBW and ABW piglets. Genes affected by birth weight were associated with pathways of translation and ribosomal activity. In conclusion, the timing of feeding high Zn concentrations to gestating sows had minimal influence on concentrations of trace minerals in sows and their offspring, while piglet birth weight may have meaningful effects on mineral metabolism and protein synthesis of neonatal piglets.