Purpose Chronic asthenia (CA) is complained by some patients that have undergone thyroid surgery. We evaluate its impact in patients undergoing unilateral or bilateral thyroidectomy, the trend during a 1-year follow-up, and the possible risk factors. Methods A prospective, cohort study was carried out on 263 patients scheduled for thyroidectomy from 2012 and 2014. Exclusion criteria were as follows: Graves' disease, malignancies requiring radioiodine therapy, post-surgical hypoparathyroidism, laryngeal nerve palsy, abnormal pre-and postoperative thyroid hormone levels, and BMI outside the normal range. Demographics; smoking and alcoholism addiction; cardiac, pulmonary, renal, and hepatic failure; diabetes; anxiety; and depression were recorded. The Brief Fatigue Inventory (BFI) was used to evaluate CA and its possible association with these comorbidities 6 and 12 months after thyroidectomy. Results One hundred seventy-seven patients underwent total thyroidectomy (TT), 54 hemithyroidectomy (HT). Thirty-two patients were not recorded because of the onset of exclusion criteria. In the 6 months after thyroidectomy, in the TT group, 64 patients (36.16%) reported an impairment in the BFI score and only 1 in the TL group. The mean BFI score changed from 1.663(±1.191) to 2.16 (±11.148) in the TT group, from 1.584 (±1.371) to 1.171 (±1.093) in the TL group (p < 0.001). No further significant variations in BFI were reported 1 year after surgery. Conclusions CA worsened after TT, but not after HT. Apart from operative procedure itself, no other risk factor was found be significantly associated with post-thyroidectomy asthenia. Further investigation is needed to determine the causes of CA.