Let \(\alpha\) and \(\beta\) be orientation-preserving diffeomorphism (shifts) of \(\mathbb{R}_+=(0,\infty)\) onto itself with the only fixed points \(0\) and \(\infty\), where the derivatives \(\alpha'\) and \(\beta'\) may have discontinuities of slowly oscillating type at \(0\) and \(\infty\). For \(p\in(1,\infty)\), we consider the weighted shift operators \(U_\alpha\) and \(U_\beta\) given on the Lebesgue space \(L^p(\mathbb{R}_+)\) by \(U_\alpha f=(\alpha')^{1/p}(f\circ\alpha)\) and \(U_\beta f=(\beta')^{1/p}(f\circ\beta)\). For \(i,j\in\mathbb{Z}\) we study the simplest weighted singular integral operators with two shifts \(A_{ij}=U_\alpha^i P_\gamma^++U_\beta^j P_\gamma^-\) on \(L^p(\mathbb{R}_+)\), where \(P_\gamma^\pm=(I\pm S_\gamma)/2\) are operators associated to the weighted Cauchy singular integral operator \[ (S_\gamma f)(t)=\frac{1}{\pi i}\int_{\mathbb{R}_+} \left(\frac{t}{\tau}\right)^\gamma\frac{f(\tau)}{\tau-t}d\tau \] with \(\gamma\in\mathbb{C}\) satisfying \(0<1/p+\Re\gamma<1\). We prove that the operator \(A_{ij}\) is a Fredholm operator on \(L^p(\mathbb{R}_+)\) and has zero index if \[ 0<\frac{1}{p}+\Re\gamma+\frac{1}{2\pi}\inf_{t\in\mathbb{R}_+}(\omega_{ij}(t)\Im\gamma), \quad \frac{1}{p}+\Re\gamma+\frac{1}{2\pi}\sup_{t\in\mathbb{R}_+}(\omega_{ij}(t)\Im\gamma)<1, \] where \(\omega_{ij}(t)=\log[\alpha_i(\beta_{-j}(t))/t]\) and \(\alpha_i\), \(\beta_{-j}\) are iterations of \(\alpha\), \(\beta\). This statement extends an earlier result obtained by the author, Yuri Karlovich, and Amarino Lebre for \(\gamma=0\).