Tumor Treating Fields (TTFields) are low intensity, intermediate frequency alternating electric fields targeting rapidly dividing cells. TTFields (200 kHz) are FDA-approved for the treatment of glioblastoma based on phase 3 studies demonstrating efficacy and high safety profile. TTFields are currently being tested as a treatment option for other solid tumors in the brain, abdomen and torso. We evaluated if the safety profile of TTFields is maintained at various frequencies in different body regions. TTFields were applied for 1-4 weeks using the Novo-TTF 100 system to: rat torso, and rabbit brain and torso, 2-3 V/cm and 150 and 200 kHz, which are intensities and frequencies known to be effective for the treatment of GBM, NSCLC, mesothelioma, pancreatic cancer, ovarian cancer and hepatocellular carcinoma. The safety of TTFields in combination with liposomal doxorubicin and cyclophosphamide or paclitaxel was tested in animals. Throughout the treatment course, all animals underwent daily clinical examination by a certified experienced veterinarian and their body weight was determined on a weekly basis. Extensive blood workup, ECG and temperature measurements were performed in the rabbit experiments. At the end of treatment, animals were euthanized and an experienced independent pathologist performed histological comparative evaluation of all major internal organs. No changes in the following parameters were observed: activity level, food intake, drinking, stools, motor neurological status and respiration. Further, no changes in weight were observed between the TTFields treated and the relevant control groups. No significant changes were observed in complete blood count and differential between TTFields treated animals and the relevant control groups. Histological analysis did not reveal any increase in pathological findings in the TTFields treated animals group. Taken together, these results demonstrate the safety of TTFields application at frequencies of 150-200 kHz to different body regions. No additional toxicities were observed with the combination of TTFields and chemotherapeutic agents vs. chemotherapy agents alone. This work further supports the high safety profile of TTFields and offer opportunities for combining TTFields with various chemotherapy agents.