Background: Amid the large panel of autoimmune thyroid diseases, Hashimoto’s thyroiditis (HT) represents a major point across multidisciplinary daily practice. When it comes to the clinical picture, particularly in regard to asthenia (also described as “fatigue” or “decreased energy”), the differential diagnosis is challenging, and a meticulous anamnesis should be backed up by focused lab investigations. Our objective was to analyze the thyroid panel in newly diagnosed patients with HT in relationship with the presence of asthenia as an admission complaint. Methods: This was a retrospective, multi-centric, real-life study conducted in secondary endocrine units (university hospitals) from July 2022 to July 2023. The exclusion criteria were COVID-19 infection; an active malignancy, etc. Results: The cohort (N = 120) included an asthenia group (AS, 49.2%) and a non-AS group of a similar age (49.3 ± 14.7 vs. 47.1 ± 14.8 y, p = 0.426). Headache was more frequent in the AS group (35.6% vs. 18%, p = 0.03). Thyroid function and HT-related antibodies assays were similar between the groups and show no correlation with serum total cholesterol and triglycerides, respectively. TSH levels did not vary among the age sub-groups (p = 0.701). One third of the studied population was affected by hypothyroidism (TSH > 4.5 μIU/mL), being seen at a higher rate in the AS (39%) vs. non-AS group (23%). Total cholesterol positively correlated with the patients’ age (r = 0.180, p = 0.049) and triglycerides (N = 120; r = 0.324, p < 0.001), as found only in the non-AS group (r = 0.246, p = 0.006, respectively, r = 0.319, p < 0.001). Conclusions: The analysis of the AS vs. non-AS group pinpointed the fact that, in regard to daily practice, asthenia as an admission complaint seems less of an indicator of an underlying thyroid dysfunction or a higher level of serum antibodies against thyroid in patients without a full clinical picture of thyrotoxicosis or myxoedema.