季节性疟疾化学预防（SMC）是降低高传播区儿童疟疾负担的重要干预措施。尼日利亚已广泛推行季节性疟疾化学预防，但儿童首日未服用磺胺多辛-乙胺嘧啶联合阿莫地喹（SPAQ）仍普遍存在。为探讨其影响因素，本研究重点分析照料者知识、社会经济状况及社区健康工作者特征对首日联合用药服用的影响。本研究使用2020至2022年尼日利亚季节性疟疾化学预防入户调查数据，共纳入30545户家庭。采用卡方检验分析首日联合用药服用与各因素的相关性，利用二元逻辑回归模型筛选关键影响因素，开展敏感性分析以验证结果稳健性，并通过结构方程模型探索相关因素间的作用路径。结果显示，首日联合用药服用率总体呈上升趋势，但2022年略有回落（2020年85.9%，2021年96.1%，2022年94.3%）。照料者教育水平、季节性疟疾化学预防知识水平及对社区健康工作者的熟悉程度均显著影响服药情况。二元逻辑回归结果表明，照料者识字能力（OR=1.76, 95% CI: 1.25–2.48）、季节性疟疾化学预防知识（OR=2.66, 95% CI: 1.92–3.67）及社区健康工作者社区融合程度（OR=2.53, 95% CI: 1.96–3.25）为服药的积极预测因素。结构方程模型分析显示，照料者知识与社区健康工作者熟悉程度对服药具有最强的直接正向效应，社会经济状况则表现出轻微负向效应。研究提示，强化照料者知识和社区健康工作者关系对提高首日联合用药服用率至关重要。应进一步加强以社区为基础的干预模式，针对性开展健康教育，以提升季节性疟疾化学预防覆盖效果。

Seasonal Malaria Chemoprevention （SMC） is a key strategy to reduce malaria burden among children aged 3–59 months in high-transmission regions, yet gaps remain in the receipt of the first dose of Sulfadoxine-Pyrimethamine plus Amodiaquine （SPAQ）, which is critical for achieving optimal protective effects. This study investigates the determinants of non-receipt of first-day SPAQ in Nigeria, with a focus on caregiver knowledge, socioeconomic factors, and distributor characteristics. Using annual end-of-round （EoR） coverage survey data from 2020 to 2022 comprising 30,545 households, we conducted descriptive analyses to track coverage trends and community health worker （CHW） visitation rates, and applied chi-square tests, logistic regression, and structural equation modeling （SEM） to examine associations and causal pathways. Sensitivity analyses were performed on subsamples stratified by caregiver refusal and caregiver/child absence to assess the robustness of key predictors. Results indicated an overall improvement in SPAQ coverage across years （from 85.9% in 2020 to 96.1% in 2021, slightly declining to 94.3% in 2022）, alongside increases in household visitation. Significant associations were observed between SPAQ receipt and caregiver education, SMC knowledge, and distributor familiarity. Regression analysis showed that caregiver literacy （OR=1.76, 95% CI: 1.25–2.48）, caregiver SMC knowledge （OR=2.66, 95% CI: 1.92–3.67）, and community affiliation of the distributor （OR=2.53, 95% CI: 1.96–3.25） were strong positive predictors of receipt. SEM further confirmed the importance of caregiver knowledge and distributor familiarity as direct influences on SPAQ receipt, while socioeconomic status exerted a weak negative effect. These findings underscore the need to strengthen community-based distribution networks, enhance intervention-specific caregiver knowledge, and tailor strategies to address both behavioral and structural barriers to improve first-day SPAQ receipt.