Serological assays are valuable tools for tracking COVID-19 spread, estimation of herd immunity, and evaluation of vaccine effectiveness. Several reports from Saudi Arabia describe optimized in-house protocols that enable detection of SARS-CoV-2 specific antibodies and measurement of their neutralizing activity. Notably, there were variations in the approaches utilized to develop and validate these immunoassays in term of sample size, validation methodologies, and statistical analyses. The developed enzyme-linked immunoassays (ELISAs) were based on the viral full-length spike (S), S1 subunit, and nucleocapsid (NP), and enabled detection of IgM and/or IgG. ELISAs were evaluated and validated against a microneutralization assay utilizing a local SARS-CoV-2 clinical isolate, FDA-approved commercially available immunoassays, and/or real-time polymerase chain reaction (RT-PCR). Overall, the performance of the described assays was high, reaching up to 100% sensitivity and 98.9% specificity with no cross-reactivity with other coronaviruses. In-house immunoassays, along with commercially available kits, were subsequently applied in a number of sero-epidemiological studies aiming to estimate sero-positivity status among local populations including healthcare workers, COVID-19 patients, non-COVID-19 patients, and healthy blood donors. The reported seroprevalence rates differed widely among these studies, ranging from 0.00% to 32.2%. These variations are probably due to study period, targeted population, sample size, and performance of the immunoassays utilized. Indeed, lack of sero-positive cases were reported among healthy blood donors during the lockdown, while the highest rates were reported when the number of COVID-19 cases peaked in the country, particularly among healthcare workers working in referral hospitals and quarantine sites. In this review, we aim to (1) provide a critical discussion about the developed in-house immunoassays, and (2) summarize key findings of the sero-epidemiological studies and highlight strengths and weaknesses of each study.