Silver-containing wound dressings are an integral part of wound therapy in adult and pediatric burn patients. The antimicrobial effect of silver is well known and has been described in numerous studies. Side effects are rarely reported from silver-containing wound care products, even though systemic absorption of silver has been shown by elevated levels of silver in the blood of patients after silver exposure during wound therapy. This animal study investigated the silver levels of blood and in which organs and tissues silver is detectable after long-term application of silver-containing wound dressings after a burn trauma. In male rats, a major full-thickness scald was created on their backs according to a standardized burn model. Two different silver-containing wound dressings (nanocrystalline silver [NCS] and silver sulphate foam [SSF]) were applied initially and changed every 7 days. Weekly blood drawings revealed an increase of blood silver in week three with significant higher values in the SSF compared with NCS group (Ag μg/kg 135.8 vs. 61.7; means; p ≤ 0.05). Thereafter, the NCS group showed significantly higher blood silver levels than the SSF group at week five (Ag μg/kg 192.3 vs. 81.3; means; p ≤ 0.01) and six (Ag μg/kg 168.2 vs. 32.9; means; p ≤ 0.01). After 6 weeks, the animals were sacrificed, and the organs and tissues were analyzed for their silver content by inductively coupled plasma mass-spectrometry. Silver was detectable in all analyzed organs and tissue samples, with higher silver values in parenchymatous organs in the NCS than SSF group (Ag μg/kg; spleen: 3,469 vs. 260; kidney: 3,186 vs. 289; liver: 2,022 vs. 313; means; p ≤ 0.05). Silver was also detectable in brain, testis, lung, heart, and muscle tissue.